ArticleLiterature Review

Interactions Between Atopic Dermatitis and Staphylococcus aureus Infection: Clinical Implications

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Abstract

Staphylococcus aureus commonly colonizes the skin of atopic dermatitis (AD) patients and contributes to the development and exacerbation of AD. Multiple factors are associated with colonization of AD skin by S. aureus, including the strength of S. aureus-corneocyte adhesion, deficiency of antimicrobial peptides, decreased levels of filaggrin and filaggrin degradation products, overexpressed Th2/Th17 cytokines, microbial dysbiosis and altered lipid profiles. S. aureus colonization on AD skin causes skin barrier dysfunction through virulence factors such as superantigens (toxins), enzymes and other proteins. Furthermore, colonization of AD skin by S. aureus exacerbates AD and may contribute to microbial dysbiosis, allergen sensitization, Th2/Th17 polarization, development of atopic march and food allergy in AD patients. Skin colonization of S. aureus, particularly methicillin-resistant S. aureus (MRSA), is one of the major challenges commonly encountered in the management of AD. Bleach bath, and topical or systemic antibiotics could be used to control S. aureus infection on AD skin. However, careful use of antibiotics is required to control the occurence of MRSA. Recently, various strategies, including microbiome transplant, monoclonal antibodies against virulent toxins, vaccines and recombinant phage endolysin, have been studied to control S. aureus infection on AD skin. Further advances in our understanding of S. aureus could provide us with ways to manage S. aureus colonization more effectively in AD patients.

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... Frontiers in Microbiology | www.frontiersin.org Since excessive skin colonization with S. aureus is common in AD and the bacteria potentially play a causative role in the development and/or exacerbation of AD (Nakamura et al., 2013;Nakatsuji et al., 2017;Kim et al., 2019), we next determined whether p4 is effective in the context of AD skin pathology. To develop an AD-like skin phenotype, mice were subjected to mechanical barrier disruption by tapestripping and repeated application of OVA. ...
... MRSA such as USA300 is the leading cause of communityacquired skin infections (Carrel et al., 2015). Likewise, AD afflicts millions worldwide (Byrd et al., 2017;Kim et al., 2019). Skin colonization with S. aureus, particularly MRSA, hampers management of AD (Kim et al., 2019). ...
... Likewise, AD afflicts millions worldwide (Byrd et al., 2017;Kim et al., 2019). Skin colonization with S. aureus, particularly MRSA, hampers management of AD (Kim et al., 2019). S. aureus colonizes the skin of a majority of AD patients (60-100%). ...
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Chemerin-derived peptide Val66-Pro85 (p4) restricts the growth of a variety of skin-associated bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). To better understand the antimicrobial potential of chemerin peptide, we compared p4 activity against MRSA in vitro to cathelicidin LL-37, one of the key endogenous peptides implicated in controlling the growth of S. aureus. The efficacy of p4 was also validated in relevant experimental models of skin pathology, such as topical skin infection with community-acquired MRSA, and in the context of skin inflammatory diseases commonly associated with colonization with S. aureus, such as atopic dermatitis (AD). We showed that p4 collaborates additively with LL-37 in inhibiting the growth of S. aureus, including MRSA, and that p4 was effective in vivo in reducing MRSA burden. p4 was also effective in reducing levels of skin-infiltrating leukocytes in S. aureus-infected AD-like skin. Taken together, our data suggest that p4 is effective in limiting S. aureus and, in particular, MRSA skin infection.
... 114,115 Risk factors for S. aureus colonization include decreased levels of filaggrin and filaggrin J Port Soc Dermatol Venereol 79(3) 2021 Epidermal Barrier Dysfunction in Atopic Dermatitis; Tiago Fernandes Gomes, Rebeca Calado, Margarida Gonçalo degradation products, lower levels of coagulase-negative Staphylococcus, altered lipid profiles, deficiency of antimicrobial peptides and overexpression of Th2 cytokines 116-119 as IL-4 and IL-13 downregulate LL-37 and HBD-3. 117 Also, fewer coagulase-negative Staphylococci, such as S. epidermidis and S. hominis, allow a shift to S. aureus predominance during AD flares. This can be reversed by topical application of coagulase-negative Staphylococcus strains and other non-pathogenic bacteria, 116,120 which also decrease SCORAD and pruritus, and alleviate cutaneous inflammation in AD. 121,122 Moreover, antimicrobial or anti-inflammatory treatment of AD flares also increases skin microbiome diversity. ...
... 120 S. aureus exotoxins increase proinflammatory cytokines and proteases that affect keratinocytes and various immune cells in AD skin. 117 Toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxins (SEA, SEB, SEC, SED), exfoliative toxins (ETA and ETB), and leucocidin, 123 behave as superantigens and induce polyclonal T and B cell proliferation and class switching to IgE and production of allergen-specific IgE in mucosal B cells, 117,124 and SEB increases IL-31 expression, involved in pruritus, inhibits keratinocyte differentiation and suppresses filaggrin expression. 117 S. aureus may impair the usual tolerance to food and enhance food sensitization. ...
... 120 S. aureus exotoxins increase proinflammatory cytokines and proteases that affect keratinocytes and various immune cells in AD skin. 117 Toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxins (SEA, SEB, SEC, SED), exfoliative toxins (ETA and ETB), and leucocidin, 123 behave as superantigens and induce polyclonal T and B cell proliferation and class switching to IgE and production of allergen-specific IgE in mucosal B cells, 117,124 and SEB increases IL-31 expression, involved in pruritus, inhibits keratinocyte differentiation and suppresses filaggrin expression. 117 S. aureus may impair the usual tolerance to food and enhance food sensitization. ...
Article
Full-text available
Impaired skin barrier is one of the hallmarks of atopic dermatitis (AD), with abnormalities in the cornified envelope, lipid lamellae, tight junctions and cutaneous microbiome. These findings are also present in nonlesional skin of AD individuals, suggesting that epidermal barrier defects may be the initial step towards the development of AD and eventually other atopic diseases (atopic march). It is currently known that pathophysiology of AD involves an interplay between this dysfunctional skin barrier and a predominantly type 2 skewed innate and adaptive immune responses, which further disrupt the skin barrier through type 2 cytokines. In this setting, there is enhanced penetration of environmental and food allergens through a deficient barrier, leading to an increased susceptibility to sensitization. During the sensitization process, thymic stromal lymphopoietin (TSLP) polarizes skin dendritic cells to a T-helper 2 response, and TSLP seems to be a key cytokine in the sensitization of food allergy, allergic asthma and rhinitis. In this review, the authors describe the current knowledge of the pathophysiology of the epidermal barrier, its disruption in AD and how it may be involved in the development of atopic comorbidities and the role of barrier repair therapy on the prevention of the atopic march progression.
... DovePress S. hominis. 18 It has been described in the past that earlylife skin colonization by S. aureus may contribute to the onset of atopic dermatitis. 18 S. aureus colonization has also been associated with asthma, food sensitization and allergy. ...
... 18 It has been described in the past that earlylife skin colonization by S. aureus may contribute to the onset of atopic dermatitis. 18 S. aureus colonization has also been associated with asthma, food sensitization and allergy. 19,20 As neither previous antibiotic treatments nor hospital admissions were associated with colonization, atopy itself seems to increase the risk for S. aureus colonization, and no other chronic conditions with frequent use of health-care services. ...
... 17 In our study, previous SSTI was a risk factor for colonization in univariate analysis but not in logistic regression analysis. Nevertheless, as patients with atopic dermatitis suffer more SSTIs than non-atopic children, 18 it is likely that atopy is the real risk factor for colonization, as we have previously mentioned. Several authors have reported that children living in crowded settings or attending school are more likely to be colonized, 15,21,22 as these settings increase human contact and the possibility of transmission. ...
Article
Full-text available
Objective: To assess the prevalence and risk factors for S. aureus and methicillin-resistant S. aureus (MRSA) nasal colonization in Spanish children. Methods: Cross-sectional study of patients <14 years from primary care centers all over Spain. Clinical data and nasal aspirates were collected from March to July 2018. Results: A total of 1876 patients were enrolled. Prevalence of S. aureus and MRSA colonization were 33% (95% CI 30.9-35.1) and 1.44% (95% CI 0.9-2), respectively. Thirty-three percent of the children (633/1876) presented chronic conditions, mainly atopic dermatitis, asthma and/or allergy (524/633). Factors associated with S. aureus colonization were age ≥5 years (OR 1.10, 95% CI 1.07-1.12), male sex (OR 1.43, 95% CI 1.17-1.76), urban setting (OR 1.46, 95% CI 1.08-1.97) and the presence of asthma, atopic dermatitis or allergies (OR 1.25; 95% CI: 1.093-1.43). Rural residence was the only factor associated with MRSA colonization (OR 3.62, 95% CI 1.57-8.36). MRSA was more frequently resistant than methicillin-susceptible S. aureus to ciprofloxacin [41.2% vs 2.6%; p<0.0001], clindamycin [26% vs 16.9%; p=0.39], and mupirocin [14.3% vs 6.7%; p=0.18]. None of the MRSA strains was resistant to tetracycline, fosfomycin, vancomycin or daptomycin. Conclusions: The main risk factors for S. aureus colonization in Spanish children are being above five years of age, male gender, atopic dermatitis, asthma or allergy, and residence in urban areas. MRSA colonization is low, but higher than in other European countries and is associated with rural settings.
... Reduced risk with perinatal and/or early-life microbial/allergen exposure [161,162] Reduced with endotoxin exposure in childhood [164] Higher abundance of certain gut bacteria was shown in asthmatic subjects [165,166] Allergic rhinitis Alteration in normal nasal mucosal bacterial abundance and diversity was shown [169,170] Reduced risk with early-life exposure to environmental microbiota [155,171] Atopic dermatitis Altered abundance and diversity of skin microbiota compared to healthy skin [131,175,176,180] Early-life skin colonization of certain bacteria in AD [182] Increased risk with dysregulated gut-skin axis [176,183,184] Filaggrin mutation can initiate AD [177][178][179] Food allergy Increased risk with dysbiosis in gut environment [189,191] Increased risk with lower gut microbiota diversity at early infancy [190] Reduced risk maternal Mediterranean diet during lactation and gestation [193] Reduced risk with diet consisting of high levels of fruits and vegetables during infancy [194] Increased risk with high-sugar, high-fat, low short-chain fatty acid diets [195] sensitization. 155 Host microbiota has been primarily linked to asthma pathogenesis via gut microbial metabolites. ...
... 172,173 It has been demonstrated several times that the composition and diversity of microorganisms on the skin differ between people with eczema and those healthy ones. 131,[174][175][176] It is a major question whether barrier disruption in the affected organs starts first or proceeds microbial dysbiosis ( Table 2). In other words, it is still unclear whether dysbiosis of the skin microbiome is one of the pathogenetic factors of AD or the cause of the onset of AD. ...
Article
Full-text available
Environmental exposure plays a major role in the development of allergic diseases. The exposome can be classified into internal (e.g., aging, hormones, and metabolic processes), specific external (e.g., chemical pollutants or lifestyle factors), and general external (e.g., broader socioeconomic and psychological contexts) domains, all of which are interrelated. All the factors we are exposed to, from the moment of conception to death, are part of the external exposome. Several hundreds of thousands of new chemicals have been introduced in modern life without our having a full understanding of their toxic health effects and ways to mitigate these effects. Climate change, air pollution, microplastics, tobacco smoke, changes and loss of biodiversity, alterations in dietary habits, and the microbiome due to modernization, urbanization, and globalization constitute our surrounding environment and external exposome. Some of these factors disrupt the epithelial barriers of the skin and mucosal surfaces, and these disruptions have been linked in the last few decades to the increasing prevalence and severity of allergic and inflammatory diseases such as atopic dermatitis, food allergy, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, and asthma. The epithelial barrier hypothesis provides a mechanistic explanation of how these factors can explain the rapid increase in allergic and autoimmune diseases. In this review, we discuss factors affecting the planet's health in the context of the 'epithelial barrier hypothesis,' including climate change, pollution, changes and loss of biodiversity, and emphasize the changes in the external exposome in the last few decades and their effects on allergic diseases. In addition, the roles of increased dietary fatty acid consumption and environmental substances (detergents, airborne pollen, ozone, microplastics, nanoparticles, and tobacco) affecting epithelial barriers are discussed. Considering the emerging data from recent studies, we suggest stringent governmental regulations, global policy adjustments, patient education, and the establishment of individualized control measures to mitigate environmental threats and decrease allergic disease.
... By far, Staphylococcus aureus (Sa) is the best characterized microorganism in AD because it is present on the skin of AD patients [20]. In fact, Sa skin-colonized AD patients have been recently shown to present a more severe form of disease than non-colonized ones [21]. ...
... In fact, Sa skin-colonized AD patients have been recently shown to present a more severe form of disease than non-colonized ones [21]. Th2 cytokines have been shown to facilitate skin colonization by Sa since they reduce the expression of natural antimicrobial peptides, thus reducing defenses against Sa infection, favoring Sa skin adherence by promoting fibronectin production [20]. ...
Article
Full-text available
Translational research has changed the understanding of AD pathogenesis beyond basic mechanisms of immunology. The study in patients of rational therapies based on targeted therapies (biologicals) provides valuable information from the patient and provides lessons of clinical immunology on clinically relevant mechanism of AD pathogenesis. AD features such as skin barrier defect, skin dysbiosis, and pruritus share a common abnormal adaptive immune response process. Skin related skin-homing CLA+CD4+ memory T cells produce IL-4, IL-13, and IL-31 which are key mediators in AD pathogenesis. Lessons learned from AD is that translation immunology allows generating rational therapies for AD and learning the immunopathogenesis in the patient
... [1][2][3] It is also the most frequent cause of infection-induced flares of atopic dermatitis (AD). [4][5][6] The bacterium expresses many virulence factors in both its cell wall and secretome. [7][8][9] Previous studies have focused on recognition of S aureus by host innate immunity, particularly activation of the inflammasome through Tolllike receptors (TLRs) and subsequent induction of cytokines such as IL-1b. ...
... 15,16 The current paradigm is that rather than a single factor, a complex array of S aureus virulence factors contributes to the atopic skin response. 4,7 However, the study of immunodeficiency and immune dysregulation disorders has taught us that there is much redundancy in host immunity. 17,18 The hypothesis we set out to explore was whether S aureus expresses a dominant virulence factor that initiates type 2-promoting cytokine release from skin cells and drives the development of AD. ...
Article
Full-text available
Background Staphylococcus aureus is the dominant infective trigger of atopic dermatitis (AD). How this bacterium drives type 2 allergic pathology in the absence of infection in patients with AD is unclear. Objective We sought to identify the S aureus–derived virulence factor(s) that initiates the cutaneous type 2–promoting immune response responsible for AD. Methods In vitro human keratinocyte cell culture, ex vivo human skin organ explants, and the eczema-prone Nishiki-nezumi Cinnamon/Tokyo University of Agriculture and Technology strain mouse were used as model systems to assess type 2–promoting immune responses to S aureus. Identification of the bioactive factor was accomplished using fast protein liquid chromatography and mass spectrometry. Bioactivity was confirmed by cloning and expression in an Escherichia coli vector system, and S aureus second immunoglobulin-binding protein (Sbi) mutant strains confirming loss of activity. Results S aureus was unique among staphylococcal species in its ability to induce the rapid release of constitutive IL-33 from human keratinocytes independent of the Toll-like receptor pathway. Using the eczema-prone Nishiki-nezumi Cinnamon/Tokyo University of Agriculture and Technology strain mouse model, we showed that IL-33 was essential for inducing the immune response to S aureus in vivo. By fractionation and candidate testing, we identified Sbi as the predominant staphylococcus-derived virulence factor that directly drives IL-33 release from human keratinocytes. Immunohistology of skin demonstrated that corneodesmosin, a component of corneodesmosomes that form key intercellular adhesive structures in the stratum corneum, was disrupted, resulting in reduction of skin barrier function. Conclusions S aureus–derived Sbi is a unique type 2–promoting virulence factor capable of initiating the type 2–promoting cytokine activity underlying AD.
... The microparticle results for AA + NIC CM 50 were confirmed by means of a diffusion disk assay, which enabled visualization of the presence of halos between 8 and 10 mm, mainly in S. aureus, which clearly showed a larger halo (13 mm) compared to the other bacteria. S. aureus is an extremely problematic pathogen, therefore formulations that inhibit the growth of this bacterial population are important adjuvants in cases of lesions involving the skin [34]. It was also possible to observe that the size of the halo for these This result was satisfactory because, in general, it can be said that there was no significant permeation of nicotinamide, which is mandatory for a cosmetic product. ...
... The microparticle results for AA + NIC CM 50 were confirmed by means of a diffusion disk assay, which enabled visualization of the presence of halos between 8 and 10 mm, mainly in S. aureus, which clearly showed a larger halo (13 mm) compared to the other bacteria. S. aureus is an extremely problematic pathogen, therefore formulations that inhibit the growth of this bacterial population are important adjuvants in cases of lesions involving the skin [34]. It was also possible to observe that the size of the halo for these bacteria during the first 12 h was 3 mm higher (data not shown) than the halo obtained at 24 h, which allows us to suggest that these microparticles would need to be supplied before the end of this period. ...
Article
Full-text available
Vitamins are widely found in nature, for example, in plants and fruits. Ascorbic acid and nicotinamide are examples of these compounds that have potent antioxidant properties, besides stimulating collagen production and depigmenting properties that protect the skin from premature aging. To overcome the skin barrier and reduce the instability of antioxidant compounds, alternative systems have been developed to facilitate the delivery of antioxidants, making them efficiently available to the tissue for an extended time without causing damage or toxicity. The objective of this study was to obtain chitosan biodegradable microparticles containing ascorbic acid and nicotinamide for topical delivery. The microparticles were obtained by spray drying and characterized chemically by means of scanning electron microscopy, infrared spectroscopy, X-ray diffraction, and differential exploratory calorimetry. The drugs were successfully encapsulated and the microparticles showed positive zeta potential. In vitro release assays showed a sustained release profile. The evaluation of ex vivo skin permeation and retention demonstrated low permeation and adequate retention of the compounds in the epidermis/dermis, suggesting the efficient delivery from the obtained microparticles. Antibacterial assays have shown that microparticles can inhibit the growth of microorganisms in a time- and dose-dependent manner, corroborating their use in cosmetic products for application on the skin
... The skin of AD individuals frequently exhibits loss of bacterial diversity and overgrowth of the pathogenic bacteria S. aureus [72]. Individuals with AD have greater skin colonization with S. aureus than healthy controls (60 to 100% vs. 5-30%, respectively) [73]. ...
... Individuals with AD have greater skin colonization with S. aureus than healthy controls (60 to 100% vs. 5-30%, respectively) [73]. In AD patients, the higher skin pH level, reduced levels of FLG and related breakdown products, and lower levels of antimicrobial peptides favor the skin colonization by S. aureus, which can promote cutaneous inflammation and AD flare-ups by causing direct proteolytic damage to the epidermal barrier and immune dysregulation [72]. ...
Article
Full-text available
Recent evidence showed that the postulated linear progression of the atopic march, from atopic dermatitis to food and respiratory allergies, does not capture the heterogeneity of allergic phenotypes, which are influenced by complex interactions between environmental, genetic, and psychosocial factors. Indeed, multiple atopic trajectories are possible in addition to the classic atopic march. Nevertheless, atopic dermatitis is often the first manifestation of an atopic march. Improved understanding of atopic dermatitis pathogenesis is warranted as this could represent a turning point in the prevention of atopic march. In this review, we outline the recent findings on the pathogenetic mechanisms leading to atopic dermatitis that could be targeted by intervention strategies for the prevention of atopic march.
... Было доказано, что у 90% таких пациентов на коже присутствует данный микроорганизм [19]. При этом преобладание S. aureus характерно для больных атопическим дерматитом не только при сравнении с относительно здоровыми людьми, но и с больными другими хроническим неинфекционными дерматозами [27]. ...
... Проблема присутствия S. aureus заключается не только в клинических проявлениях инфекции и высоком уровне антибиотикорезистентности, но и в выраженной иммуногенности данного микроорганизма. Так, S. aureus продуцирует энтеротоксины, которые, выступая в качестве суперантигена, разрушают кожный барьер за счет стимуляции апоптоза кератиноцитов и усиливают воспаление [27]. Кроме этого, суперантигены способствуют снижению выработки в коже IF-γ и TNF-α, которые являются важными медиаторами клеточного антибактериального и противовирусного иммунитета [28]. ...
Article
Atopic dermatitis is a chronic inflammatory skin disease linked to a genetic predisposition and accompanied by acute inflammatory manifestations that develop due to abnormality of skin barrier properties and changes in both innate and adaptive immune responses. The high risk of developing complications of this disease caused by skin and systemic infections is one of the most urgent problems of modern health care. However, infectious complications of atopic dermatitis may include skin and soft tissue infections, herpetic eczema, bacteremia, osteoarthritis, myelitis, septic arthritis, and endocarditis. Skin barrier defects, type 2 immune-mediated inflammation, Staphylococcus aureus colonization, and skin dysbiosis are main predisposing factors for an increased incidence of infectious complications of atopic dermatitis. The development of infectious complications of atopic dermatitis may be prevented by comprehensive treatment of exacerbations of the underlying disease, sanitation of chronic infection foci, as well as restoration and maintenance of the skin barrier function. The use of special moisturizers and emollients for skin care during exacerbation and remission is an important and integral part of therapeutic and preventive measures. Emollients are medical cosmetic products that are close to the natural lipid skin barrier in composition. They not only effectively soften and moisturize the skin, but also restore damaged protective properties. Additional components of emollients with anti-inflammatory and antimicrobial activity are an optional, but desirable condition to prevent recurrence of the disease and reduce the risk of developing a secondary infection. Thus, not only special skin care drugs, but also products for patients with atopic dermatitis, can contribute to the development of antibacterial protection and prevent the development of infectious complications.
... In Korea, a nationwide population-based epidemiologic survey using questionnaires of the International Study of Asthma and Allergies in Childhood (ISAAC) showed that the prevalence of "eczema treatment in the last 12 months" in 6-7 and 12-13 year-old children increased from 11.9% in 2000 to 15.3% in 2010 and from 7.4% in 2000 to 8.9% in 2010, respectively. 7,8 In contrast, data from the Korean National Health Insurance Service (NHIS) demonstrated that the estimated prevalence of AD in [6][7][8][9][10][11][12][13][14][15][16][17][18] year-old children and adolescents was lower than that from the questionnaire survey. 9,10 It is highly likely that AD prevalence based on NHIS data is underestimated, considering the fact that there are patients who receive alternative medicine or cannot receive medical services. ...
... AD severity is related to recurrent flares due to various host and environmental factors that include allergens, skin infection or colonization, meteorological factors, environmental pollution, and emotional stress. 2,[15][16][17][18] Although the direct causal relationship was not investigated in the present study, several changes Korean children have faced over the past decades should be noted. According to the Korean climate change assessment report 2020, 19 climate change is under way in the Korean peninsula as the concentration of greenhouse gases, especially CO 2 , has increased between 2008 and 2018. ...
Article
This study aimed to explore time trends in the prevalence of atopic dermatitis (AD) according to age in Korean children. We observed changes in the estimated annual prevalence of AD using data from the Korean National Health Insurance Service (NHIS) and Statistics Korea between 2003 and 2018. In each year, the highest prevalence was evident among children aged 12 to 23 months, and then the prevalence decreased with age. The annual prevalence of AD in Korean children under the age of 18 slightly increased from 4.0% in 2003 to 4.5% in 2018. During this period, the prevalence in children aged 6 to 18 years increased from 1.9% in 2003 to 3.1% in 2018, while that of infants aged less than 24 months substantially decreased. Among children who were born in 1991, 1997, 2000, 2003 and 2006, the slopes of decreasing trend lines over age 6 were similar. Comparing children born in 2009 and 2012 with those born before 2006, the more recent the birth year, the higher the prevalence of AD over age 6. In conclusion, time trends of the annual prevalence of AD in Korean children from 2003 through 2018 were different according to age group. These results suggest that AD development during infancy is decreasing whereas either a late-onset AD or early-onset, persistent phenotype is likely to increase. Different strategies according to age are required for more effective prevention and treatment of AD in Korean children.
... Reduced risk with perinatal and/or early-life microbial/allergen exposure [161,162] Reduced with endotoxin exposure in childhood [164] Higher abundance of certain gut bacteria was shown in asthmatic subjects [165,166] Allergic rhinitis Alteration in normal nasal mucosal bacterial abundance and diversity was shown [169,170] Reduced risk with early-life exposure to environmental microbiota [155,171] Atopic dermatitis Altered abundance and diversity of skin microbiota compared to healthy skin [131,175,176,180] Early-life skin colonization of certain bacteria in AD [182] Increased risk with dysregulated gut-skin axis [176,183,184] Filaggrin mutation can initiate AD [177][178][179] Food allergy Increased risk with dysbiosis in gut environment [189,191] Increased risk with lower gut microbiota diversity at early infancy [190] Reduced risk maternal Mediterranean diet during lactation and gestation [193] Reduced risk with diet consisting of high levels of fruits and vegetables during infancy [194] Increased risk with high-sugar, high-fat, low short-chain fatty acid diets [195] sensitization. 155 Host microbiota has been primarily linked to asthma pathogenesis via gut microbial metabolites. ...
... 172,173 It has been demonstrated several times that the composition and diversity of microorganisms on the skin differ between people with eczema and those healthy ones. 131,[174][175][176] It is a major question whether barrier disruption in the affected organs starts first or proceeds microbial dysbiosis ( Table 2). In other words, it is still unclear whether dysbiosis of the skin microbiome is one of the pathogenetic factors of AD or the cause of the onset of AD. ...
Article
Full-text available
Environmental exposure plays a major role in the development of allergic diseases. The exposome can be classified into internal (e.g., ageing, hormones, and metabolic processes), specific external (e.g., chemical pollutants or lifestyle factors), and general external (e.g. broader socioeconomic and psychological contexts) domains, all of which are interrelated. All the factors we are exposed to, from the moment of conception to death, are part of the external exposome. Several hundreds of thousands of new chemicals have been introduced in modern life without our having a full understanding of their toxic health effects and ways to mitigate these effects. Climate change, air pollution, microplastics, tobacco smoke, changes and loss of biodiversity, alterations in dietary habits and the microbiome due to modernization, urbanization, and globalization constitute our surrounding environment and external exposome. Some of these factors disrupt the epithelial barriers of the skin and mucosal surfaces, and these disruptions have been linked in the last few decades to the increasing prevalence and severity of allergic and inflammatory diseases such as atopic dermatitis, food allergy, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, and asthma. The epithelial barrier hypothesis provides a mechanistic explanantion of how these factors can explain the rapid increase in allergic and autoimmune diseases. In this review, we discuss factors affecting the planet's health in the context of the "epithelial barrier hypothesis", including climate change, pollution, changes and loss of biodiversity, and emphasize the changes in the external exposome in the last few decades and their effects on allergic diseases. In addition, the roles of increased dietary fatty acid consumption and environmental substances (detergents, airborne pollen, ozone, microplastics, nanoparticles, tobacco) affecting epithelial barriers are discussed. Considering the emerging data from recent studies, we suggest stringent governmental regulations, global policy adjustments, patient education and the establishment of individualized control measures to mitigate environmental threats and decrease allergic disease.
... S. aureus colonization of the lesioned skin in AD is closely related to exacerbation of the condition. Many investigators have demonstrated that S. aureus on the skin is involved in the induction of allergic immune responses and subsequent pathogenesis of AD. [11][12][13] As AD is an allergic condition, affected patients show a notable increase of Th2 cells in both the peripheral blood and skin lesions. 1) Therefore, it has been suggested that the Th2 immune response plays an important pathogenetic role in AD, and this notion is supported by the fact that most AD patients show blood eosinophilia, increased serum IgE levels and elevated IL-31 production. [14][15][16] IL-31 is known to be one of the Th2 cytokines causing the itch-associated scratching behavior of AD patients as well as NC/Nga mice, an model animal of AD. 17,18) However, it is unclear what augments IL-31 production in AD patients, and the relationship between S. aureus colonization and scratching behavior in AD patients has not yet been clarified. ...
Article
Our previous study showed that chronic skin colonization by Staphylococcus aureus exacerbated atopic dermatitis (AD) and that control of such skin colonization using antibiotic ointment might relieve AD-related skin inflammation. However, the role of S. aureus colonization in the pruritus accompanying AD was not elucidated. The aim of the present study was to evaluate the effect of topically applied josamycin, a macrolide antibiotic, on the scratching behavior of NC/Nga mice with AD-like skin lesions. Josamycin (0.1%) was topically administered to NC/Nga mice with AD-like skin lesions induced by a mite antigen, Dermatophagoides farinae extract, and the therapeutic effects of josamycin were assessed by measurement of the skin severity score, S. aureus colonization, scratching count, and interleukin (IL)-31 mRNA expression in the skin lesions. Topical treatment with josamycin ointment significantly suppressed the increase of the skin severity score in NC/Nga mice. This suppressive effect was associated with decreases in the S. aureus count on the lesioned skin, scratching behavior of mice and IL-31 mRNA expression in the lesions. The present results show that the severity of AD-like skin inflammation in NC/Nga mice is correlated with the level of S. aureus colonization and subsequent IL-31 production in the skin. Therefore, topical application of josamycin to AD lesions colonized by S. aureus would be beneficial for control of AD by eliminating superficially located S. aureus and by suppressing the IL-31-induced scratching behavior. Fullsize Image
... Atopic dermatitis is a chronic recurrent highly itchy inflammatory skin disease and a prelude to the development of food allergies, asthma or allergic rhinitis. Skin infections caused by S. aureus exacerbate skin diseases in patients with atopic dermatitis and change host response to environmental allergens and viral pathogens, which may be due to both the damaged skin barrier and impaired host immune responses (Aziz et al. 2020;Kawakami et al. 2009;Kim et al. 2019). Significant evidences indicated that SAg plays an important role in exacerbating the disease (Aziz et al. 2020;Schlievert et al. 2010). ...
Article
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Staphylococcal superantigen (SAg) toxins are the most notable virulence factors associated with Staphylococcus aureus , which is a pathogen associated with serious community and hospital acquired infections in humans and various diseases in animals. Recently, SAg toxins have become a superfamily with 29 types, including staphylococcal enterotoxins (SEs) with emetic activity, SE-like toxins (SEls) that do not induce emesis in primate models or have yet not been tested, and toxic shock syndrome toxin-1 (TSST-1). SEs and SEls can be subdivided into classical types (SEA to SEE) and novel types (SEG to SElY, SE01, SE02, SEl26 and SEl27). The genes of SAg toxins are located in diverse accessory genetic elements and share certain structural and biological properties. SAg toxins are heat-stable proteins that exhibit pyrogenicity, superantigenicity and capacity to induce lethal hypersensitivity to endotoxin in humans and animals. They have multiple pathogenicities that can interfere with normal immune function of host, increase the chances of survival and transmission of pathogenic bacteria in host, consequently contribute to the occurrence and development of various infections, persistent infections or food poisoning. This review focuses on the following aspects of SAg toxins: (1) superfamily members of classic and novelty discovered staphylococcal SAgs; (2) diversity of gene locations and molecular structural characteristics; (3) biological characteristics and activities; (4) multi-pathogenicity of SAgs in animal and human diseases, including bovine mastitis, swine sepsis, abscesses and skin edema in pig, arthritis and septicemia in poultry, and nosocomial infections and food-borne diseases in humans.
... In order to evaluate potential effects on the skin microbiota, four bacterial species were studied: S. epidermidis, S. aureus, Corynebacterium xerosis and Cutibacterium acnes. While these species are considered as skin commensals, three of them are associated with cutaneous disorders: S. epidermidis and C. acnes are involved in acne and S. aureus is an opportunistic pathogen that is responsible for skin infections and suspected to contribute to the exacerbation of atopic dermatitis [22][23][24]. To date, few biological evaluations have been reported on hydrophobic DES. ...
Article
Microalgae are a sustainable source of bioactive compounds like carotenoids, free fatty acids and especially polyunsaturated fatty acids. The extraction of such nonpolar metabolites usually involved nonpolar or toxic solvent like methanol or hexane. We report the first screening of Natural Deep Eutectic Solvents for the extraction of pigments and free fatty acids from spirulina. Natural Deep Eutectic Solvent with a wide range of polarity was screened, and the resulting extracts were compared according to their pigment and free fatty acid contents. The extraction performance was increased, and various metabolite profiles were obtained. A Natural Deep Eutectic Solvent based on glycerol/glucose exhibited a wide range of metabolites, which ranged from polar phycobiliproteins to free fatty acids. Natural Deep Eutectic Solvent based on a fatty acid mixture demonstrated the highest selectivity towards free fatty acids. After intensification of the extraction process, 6 spirulina- Natural Deep Eutectic Solvent formulations and Natural Deep Eutectic Solvent alone were evaluated in terms of the effects on cutaneous inflammation induced by Staphylococcus aureus, as well on 4 bacterial species that are part of the skin microbiota. The glycerol/glucose formulation exhibited an anti-inflammatory effect on keratinocytes stimulated by S. aureus. Nonpolar Natural Deep Eutectic Solvent alone and formulations impacted bacterial viability, especially for S. aureus, thus providing a new approach for the regulation of skin microbiota or product preservation.
... These bacteria have anti-inflammatory effects and help prevent the proliferation of pathogenic bacteria such as S. aureus strains, thereby acting as a skin barrier [4]. They also produce various bacteriocins-antibacterial peptides-to prevent the colonization and proliferation of pathogenic bacteria and the subsequent production of proinflammatory cytokines, and to strengthen the skin barrier to maintain skin homeostasis [54][55][56]. ...
Article
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Atopic dermatitis (AD) is a refractory and relapsing skin disease with a complex and multifactorial etiology. Various congenital malformations and environmental factors are thought to be involved in the onset of the disease. The etiology of the disease has been investigated, with respect to clinical skin symptoms and systemic immune response factors. A gut microbiome–mediated connection between emotional disorders such as depression and anxiety, and dermatologic conditions such as acne, based on the comorbidities of these two seemingly unrelated disorders, has long been hypothesized. Many aspects of this gut–brain–skin integration theory have recently been revalidated to identify treatment options for AD with the recent advances in metagenomic analysis involving powerful sequencing techniques and bioinformatics that overcome the need for isolation and cultivation of individual microbial strains from the skin or gut. Comparative analysis of microbial clusters across the gut–skin axis can provide new information regarding AD research. Herein, we provide a historical perspective on the modern investigation and clinical implications of gut–skin connections in AD in terms of the integration between the two microbial clusters.
... Infants with S aureus colonization or who lack S aureuseinhibiting commensals 39 at 3 months are more likely to develop AD compared with those who are not colonized. 63 Various S aureus virulence factors have been associated with AD. 66,67 The S aureus cell wall component lipoteichoic acid upregulates over 300 genes in keratinocytes, including T H 2-polarizing genes, such as TSLP and IL-4. In addition, lipoteichoic acid reduces FLG expression. ...
Article
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Objective: To discuss the skin microbiome modulates immunity by interactions between skin immunology with keratinocytes to combat pathogens. Allergic disorders are classified by immunoglobulin E sensitivity and aberrant TH2 cell responses, and an increasing number of studies have described the associations with skin microbiome fluctuations. In this review, we discuss commensal-epidermal homeostasis and its influence on allergic disease. Data sources: All included references were obtained from the PubMed database. Study selections: Studies addressing relevant aspects of commensal-epidermal homeostasis, skin microbiome dysbiosis, microbiome-targeted therapeutics, and prevention in allergy were included. Results: Homeostasis between the commensal microbiome and the epidermis is important in protecting against allergic disease. Commensals promote antiallergic TH1 and TH17 immunophenotypes within the skin and induce keratinocytes to secrete antimicrobial peptides and alarmins that enhance barrier function and antagonize proallergic organisms. Perturbations in this homeostasis, however, is associated with allergic disease development. Atopic dermatitis is associated with decreases in skin commensals and increases in the pathogen, Staphylococcus aureus. Fluctuations in the skin microbiome contributes to decreased barrier dysfunction, allergic sensitization, and TH2 cytokine secretion. Little is known about how the skin microbiome affects food allergy, allergic rhinitis, and asthma, and it is poorly understood how cutaneous inflammation influences systemic allergic responses. Therapies are targeted toward maintenance of the skin barrier, replacement of healthy commensals, and anti-TH2 biologic therapy. Conclusion: Although the effects of commensal-epidermal homeostasis on allergy within the skin are becoming increasingly clear, future studies are necessary to assess its effects on extracutaneous allergic disorders and explore potential therapeutics targeting the skin microbiome.
... The skin barrier defects in patients with AD have been attributed to loss-of-function mutations and/or decreased expression of filaggrin as well as other components that maintain the epidermal barrier (e.g., loricrin and involucrin) (7,8). The affected skin of patients with AD also has markedly increased Staphylococcus aureus colonization that further exacerbates skin inflammation through the activity of S. aureus-derived cytolytic toxins, superantigens, and proteases (9)(10)(11). In this setting of skin barrier defects and dysbiosis in AD, there is also markedly increased production of IL-33, thymic stromal lymphopoietin (TSLP), and IL-25 that skew the immune response toward type 2 immunity with increased IgE production and allergic inflammation by activating dendritic cells, Th2 cells, group 2 innate lymphoid cells (ILC2s), mast cells, eosinophils, and basophils (2)(3)(4). ...
Article
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IgE induced by type 2 immune responses in atopic dermatitis is implicated in the progression of atopic dermatitis to other allergic diseases, including food allergies, allergic rhinitis, and asthma. However, the keratinocyte-derived signals that promote IgE and ensuing allergic diseases remain unclear. Herein, in a mouse model of atopic dermatitis-like skin inflammation induced by epicutaneous Staphylococcus aureus exposure, keratinocyte release of IL‑36α along with IL-4 triggered B cell IgE class-switching, plasma cell differentiation, and increased serum IgE levels-all of which were abrogated in IL-36R-deficient mice or anti-IL‑36R-blocking antibody-treated mice. Moreover, skin allergen sensitization during S. aureus epicutaneous exposure-induced IL-36 responses was required for the development of allergen-specific lung inflammation. In translating these findings, elevated IL‑36 cytokines in human atopic dermatitis skin and in IL‑36 receptor antagonist-deficiency patients coincided with increased serum IgE levels. Collectively, keratinocyte-initiated IL‑36 responses represent a key mechanism and potential therapeutic target against allergic diseases.
... Notably, neutrophils are recognized to for their importance in healing tissue injury 55 and in host defence against microbial pathogens including S. aureus 56 . As AD skin is commonly colonized with S. aureus, one may expect that neutrophils and their derived IL-1β act as double-sided sword, on the one hand contributing to S. aureus clearance, and on the other hand, as shown in this study, contributing to the promotion and exacerbation of skin allergic sensitization, which provides one plausible explanation for the association of S. aureus in AD with the development of atopic march 57 . In keeping with our data, an early recruitment of neutrophils was shown to promote contact allergic sensitization of hapten 21 . ...
Article
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Atopic diseases, including atopic dermatitis (AD) and asthma, affect a large proportion of the population, with increasing prevalence worldwide. AD often precedes the development of asthma, known as the atopic march. Allergen sensitization developed through the barrier-defective skin of AD has been recognized to be a critical step leading to asthma, in which thymic stromal lymphopoietin (TSLP) was previously shown to be critical. In this study, using a laser-assistant microporation system to disrupt targeted skin layers for generating micropores at a precise anatomic depth of mouse skin, we model allergen exposure superficially or deeply in the skin, leading to epicutaneous sensitization or dermacutaneous sensitization that is associated with a different cytokine microenvironment. Our work shows a differential requirement for TSLP in these two contexts, and identifies an important function for IL-1β, which is independent of TSLP, in promoting allergen sensitization and subsequent allergic asthma.
... The role of Th1-mediated immunity is less clear, as several studies have demonstrated a protective role for this subset in mouse models, but several groups have also reported that Th1-mediated responses may also inhibit protective immunity (53,88,89). A role for Th2 responses has been established in allergic diseases mediated by S. aureus (90). While Th22 responses may complement Th17-mediated protection at the mucocutaneous interface (91), the role of this subset is less well-defined. ...
Article
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Recurrent S. aureus infections are common, suggesting that natural immune responses are not protective. All candidate vaccines tested thus far have failed to protect against S. aureus infections, highlighting an urgent need to better understand the mechanisms by which the bacterium interacts with the host immune system to evade or prevent protective immunity. Although there is evidence in murine models that both cellular and humoral immune responses are important for protection against S. aureus, human studies suggest that T cells are critical in determining susceptibility to infection. This review will use an “anatomic” approach to systematically outline the steps necessary in generating a T cell-mediated immune response against S. aureus. Through the processes of bacterial uptake by antigen presenting cells, processing and presentation of antigens to T cells, and differentiation and proliferation of memory and effector T cell subsets, the ability of S. aureus to evade or inhibit each step of the T-cell mediated response will be reviewed. We hypothesize that these interactions result in the redirection of immune responses away from protective antigens, thereby precluding the establishment of “natural” memory and potentially inhibiting the efficacy of vaccination. It is anticipated that this approach will reveal important implications for future design of vaccines to prevent these infections.
... In some skin diseases, there is an inverse correlation between the severity of the disease and the level of antimicrobial peptide production. 6 The human β-defensins (hBDs) are found primarily in epithelial cells and numerous sites throughout the body. 7,8 DEFB1 is generally transcribed at a constitutive low level in epithelial cells. ...
Article
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Objective: To study the relationship between the single nucleotide polymorphisms (SNPs) of the human β-defensin 1-gene (DEFB1) and the genetic susceptibility of acne vulgaris in the Han Chinese ethnic group. Methods: A total of 104 patients with acne vulgaris and 126 healthy participants were included in our study. We analyzed the association between acne vulgaris and the polymorphisms in the DEFB1 G-52A, C-44G, and G-20A gene. We then analyzed the relationship between the different genotypes and the susceptibility to acne vulgaris. Results: The frequency of DEFB1 C-44G genetic polymorphisms between the acne vulgaris group and the control group was significantly different (P < 0.05). The frequency of DEFB1 G-20A genetic polymorphisms between the acne vulgaris group and the control group was also significantly different (P < 0.05). Conclusion: The -44G or -20A allele showed a low expression in acne vulgaris, which has already been shown to correlate with the low risk of acne vulgaris among Chinese Han patients. This further supports the contribution of the DEFB1 gene to the pathogenesis of acne.
... Нарушение функции эпидермального барьера приводит к повышению проницаемости эпидермиса, транскутанному проникновению аллергенов и микробов, что обуславивает нарушение микробиома кожи за счет чрезмерной колонизации патогенными микроорганизмами -S. aureus, грибами Malassezia spp., Candida spp., вирусом простого герпеса и др., которые способны, как и аллергены, вызывать и поддерживать персистирующее воспаление в коже больных АД [6][7][8][9][10]. ...
Article
Atopic dermatitis is a multifactorial genetic inflammatory skin disease associated with disturbances of skin barrier function affected by predisposition to IgE-mediated hypersensitivity, which is characterized by itching, chronic recurrent course of the disease, age-related features of localization and lesion morphology, and requires the long-term and permanent treatment.Treatment is based on the continuous use of emollients, topical calcineurin inhibitors, topical glucocorticoids, and hygienic skin care.The mechanisms of the atopic dermatitis development are primarily based on a genetic predisposition to allergies, failure of the normal development of congenital and acquired factors of the immune system, as well as the influence of environmental factors and various trigger factors, such as allergenic (food, indoor, epidermal, fungal allergens, etc.). and non-allergenic (tobacco smoke, pollutants, psycho-emotional stress, concomitant chronic and acute diseases, mainly ARVI, etc.).It has been established that atopic dermatitis is characterized by the epidermal barrier dysfunction leading to excessive tran-sepidermal water loss, increased permeability of the epidermis, the penetration of allergens and microbial agents via the skin and eventually to sensitization to allergens and the development of specific allergic skin inflammation and atopic march with the sequential development of other atopic diseases.Modern therapeutic strategies are actively aimed at repairing the epidermal barrier, preventing sensitization and atopic march development. This article describes the features of the epidermal barrier dysfunction in atopic dermatitis, lists the methods of its restoration and ways to prevent subsequent exacerbations using local therapy and emollients, and presents 3 clinical cases.
... Impetigo is easily diagnosed by the yellow crusts and can be treated with fusidic acid, topical mupirocin or topical retapamulin for 5 days. 198 The high rate of S. aureus resistance against fusidic acid in Europe compared with the United States reflects the more frequent use in Europe. 199 Systemic antibiotics should only be used in case of apparent and extensive bacterial superinfection. ...
Article
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Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease. The diagnosis is made using evaluated clinical criteria. Disease activity and burden are best measured with a composite score, assessing both objective and subjective symptoms, such as SCORing Atopic Dermatitis (SCORAD). AD management must take into account clinical and pathogenic variabilities, the patient’s age and also target flare prevention. Basic therapy includes hydrating and barrier‐stabilizing topical treatment universally applied, as well as avoiding specific and unspecific provocation factors. Visible skin lesions are treated with anti‐inflammatory topical agents such as corticosteroids and calcineurin inhibitors (tacrolimus and pimecrolimus), which are preferred in sensitive locations. Topical tacrolimus and some mid‐potency corticosteroids are proven agents for proactive therapy, which is defined as the long‐term intermittent anti‐inflammatory therapy of frequently relapsing skin areas. Systemic anti‐inflammatory or immunosuppressive treatment is a rapidly changing field requiring monitoring. Oral corticosteroids have a largely unfavourable benefit–risk ratio. The IL‐4R‐blocker dupilumab is a safe, effective and licensed, but expensive, treatment option with potential ocular side‐effects. Other biologicals targeting key pathways in the atopic immune response, as well as different Janus kinase inhibitors, are among emerging treatment options. Dysbalanced microbial colonization and infection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R‐blockers) only have limited effects on AD‐related itch and eczema lesions. Adjuvant therapy includes UV irradiation, preferably narrowband UVB or UVA1. Coal tar may be useful for atopic hand and foot eczema. Dietary recommendations should be patient‐specific, and elimination diets should only be advised in case of proven food allergy. Allergen‐specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress‐induced exacerbations. Efficacy‐proven 'Eczema school' educational programmes and therapeutic patient education are recommended for both children and adults.
... Moreover, bacteria are likely to promote delayed healing by inflammatory processes [27]. Numerous studies showed that the microbiota plays a key role in atopic dermatitis, specifically involving Staphylococcus Aureus, which is significantly more prevalent in the inflamed skin of patients [28,29]. ...
Article
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Background: Chronic venous disease (CVD) is secondary to venous hypertension, leading to vascular inflammation and tissue changes. The impact of CVD on skin structure and barrier function is not well characterized. Objectives: We aimed to assess the characteristics of skin alterations in mild-to-moderate CVD by non-invasive techniques based on a prospective exploratory study. Material and methods: Female subjects (30-75 years) with CVD (Stage C2 to C4, CEAP classification) were eligible. Stage C0-C1 CVD subjects were used as controls. Women with leg surgery or a medical history that could impact the results were excluded. The skin changes on lesional (LS) and non-lesional (NLS) areas were assessed by biometric analysis including skin echography, viscoelasticity evaluation, confocal microscopy and trans epidermal water loss (TEWL) measurements. Results: Thirty-four subjects were enrolled. Based on computation of 26 biometric parameters using Principal Component Analysis, a significant difference between LS and NLS zones, regardless of the CEAP class, was evidenced. C2-C4 subjects presented with dermal thickening suggesting oedema associated with decreased cell density, while no difference in skin viscoelasticity was observed compared to the C0-C1 control group. Epidermal structural modifications were associated with increased TEWL correlating with CVD severity. Conclusion: Skin alterations in CVD patients are detectable by non-invasive methods. These findings may help to better assess new therapeutic strategies.
... Pathogénèse de la dermatite atopique et implication de S. aureus et S. epidermidisAMP : peptides antimicrobiens ; PDF : produits de dégradation de la filaggrine. Modifié d'aprèsKim et al. (2019). ...
Thesis
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Les ulvanes sont des polysaccharides matriciels sulfatés constitutifs de la paroi de l’algue verte Ulva sp.. Bien que proliférative et quantitativement disponible, Ulva sp. est peu valorisée avec des applications dans des domaines à faible valeur ajoutée. Ce projet de thèse a pour objectif la production de fractions enrichies en ulvanes et en oligo-ulvanes dans le but d’évaluer leurs propriétés biologiques sur le système cutané. Les fractions d’ulvanes ont été produites par macération et extraction assistée par enzyme suivie de différents procédés de purification : précipitation éthanolique et dialyse. Des dépolymérisations radicalaire et acide ont permis d’obtenir des fractions d’oligo-ulvanes. Ces fractions d’ulvanes et d’oligo-ulvanes stimulent la prolifération de fibroblastes dermiques humains. Une augmentation de la synthèse protéique de composants matriciels dont les collagènes de type I et III, et les glycosaminoglycanes a été mise en évidence. Les fractions stimulent également l’expression, la synthèse et l’activité enzymatique de MMP-1. Au niveau du microbiote cutané, ces fractions n’altèrent pas la croissance des bactéries commensales S. epidermidis, S. aureus et C. acnes, mais peuvent modifier la formation de biofilm. Les fractions d’ulvanes et d’oligo-ulvanes diminuent également le potentiel inflammatoire des kératinocytes HaCaT induit par C. acnes. Ainsi, les travaux ont démontré que les fractions d’ulvanes et d’oligo-ulvanes présentent des activités biologiques prometteuses pour des applications dermo-cosmétiques dans le cadre de stratégies de réparation tissulaire, anti-vieillissement, ou anti-inflammatoire, dans le respect du microbiote commensal cutané.
... 1,2 AD appears to be initiated and maintained by the complex interactions among genetic predisposition, environmental triggers, immune dysfunction, hypersensitivity reactions, and skin barrier defects. 3,4 The standard medical treatment for AD is topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs), which relieve symptoms and skin inflammation. However, their clinical efficacy is transient, limited, and often disappointing to many patients with AD and physicians. ...
Article
Purpose: Dupilumab is recommended to be administered biweekly to treat adult patients with moderate-to-severe atopic dermatitis (AD). Real clinical practice data on the clinical efficacy of monthly dupilumab therapy are limited. We analyzed real clinical practice data on the clinical efficacy of monthly dupilumab therapy and predictive markers for favorable clinical responses to the therapy. Methods: Medical records of 57 adult patients with moderate-to-severe AD who received dupilumab therapy every 4 weeks for 16 weeks were analyzed retrospectively. Eczema Area and Severity Index (EASI) were recorded at baseline and week 16. Clinical responses to monthly dupilumab therapy were defined as the proportion of patients with decreased EASI scores of at least 50% or 75% from baseline at week 16 (EASI-50 or EASI-75). Blood eosinophil counts and serum lactate dehydrogenase (LDH) levels were measured at baseline and week 16. Results: Monthly dupilumab therapy showed EASI-50 and EASI-75 clinical responses in 48 (84.2%) and 27 (47.4%) of 57 patients at week 16, respectively. The percentage decrease in EASI scores from baseline at week 16 was significantly inversely correlated with baseline blood eosinophil count (correlation coefficient [r] = -0.405, P = 0.002) and baseline serum LDH level (r = -0.466, P < 0.001). The EASI-75 response rate was higher in patients with low (< 500/µL, 73.3%) than in those with high (≥ 500/µL, 37.5%) baseline blood eosinophil counts (P = 0.032), and was higher in patients with low (< 400 U/L, 55.6%) than those with high (≥ 400 U/L, 10.0%) baseline serum LDH levels (P = 0.013). Conclusions: Monthly dupilumab therapy was clinically effective in adult patients with moderate-to-severe AD in real clinical practice. Baseline blood eosinophil count and serum LDH level could be predictive markers for clinical response to dupilumab therapy.
... Other commensal bacteria, such as Staphylococcus epidermidis (S. epidermidis) and Staphylococcus hominis, are also able to modulate the development of skin T cells, inhibit inflammation and prevent skin infection by producing antimicrobial peptides (AMPs) [65]. Streptococcuss Spp. and S. aureus can coexist in 70-80% of skin cultures from patients with AD and infected lesions [66,67]. ...
Article
Full-text available
Currently, there are a few detailed guidelines on the overall management of children and adolescents with moderate-severe atopic dermatitis. AD is a complex disease presenting with different clinical phenotypes, which require an individualized and multidisciplinary approach. Therefore, appropriate interaction between primary care pediatricians, pediatric allergists, and pediatric dermatologists is crucial to finding the best management strategy. In this manuscript, members of the Italian Society of Pediatric Allergology and Immunology (SIAIP), the Italian Society of Pediatric Dermatology (SIDerP), and the Italian Society of Pediatrics (SIP) with expertise in the management of moderate-severe atopic dermatitis have reviewed the latest scientific evidence in the field. This narrative review aims to define a pathway to appropriately managing children and adolescents with moderate-severe atopic dermatitis.
... The estimated prevalence of AD in Korean children aged 18 years or younger in 2014 was about 6% [8]. One basic principle in the management of AD is avoiding aggravating factors such as microbes, allergens, emotional stress, meteorological factors, and pollutants such as PMs [3,9,10]. ...
Article
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This study aimed to investigate the short-term effect of exposure to indoor fine particulate matter (PM2.5) on atopic dermatitis (AD) symptoms in children. Sixty-four children (40 boys and 24 girls) with moderate-to-severe AD, aged under 18 years were enrolled in the study. They were followed up from February 2019 through November 2020. Exposure to indoor PM2.5 in each household of the enrolled children and their AD symptoms were measured daily. The generalized linear mixed model was utilized for statistical analysis. Subdivision analysis was performed by stratifying the patients by age, sex, season, severity, the presence of family allergic diseases, sensitization, and indoor environment conditions including temperature and relative humidity. A total of 9,321 person-days of AD symptom data were collected. The average PM2.5 concentration was 28.7 ± 24.3 µg/m3, with the highest value in winter (47.1 ± 29.6 µg/m3). The overall effect of PM2.5 on AD symptoms was not statistically significant. However, an increase of 10 µg/m3 in indoor PM2.5 concentration increased AD symptom scores by 16.5% (95% CI: 6.5, 27.5) in spring and12.6% (95% CI: 4.3, 21.5) in winter, 6.7% (95% CI: 2.3, 11.3) at indoor temperatures of
... Filaggrin breakdown products in non-lesional skin of AD FA+ children were significantly lower than those on AD FA− and NA, suggesting that the stratum corneum of non-lesional skin in AD FA+ children has unique properties [58]. Furthermore, S. aureus superantigens can generate a powerful immune response; non-specific activation of T cells and IgE-mediated downstream inflammatory responses are parts of this response [59,60]. ...
Article
Full-text available
Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense pruritus, eczematous lesions, and relapsing course. It presents with great clinical heterogeneity, while underlying pathogenetic mechanisms involve a complex interplay between a dysfunctional skin barrier, immune dysregulation, microbiome dysbiosis, genetic and environmental factors. All these interactions are shaping the landscape of AD endotypes and phenotypes. In the “era of allergy epidemic”, the role of food allergy (FA) in the prevention and management of AD is a recently explored “era”. Increasing evidence supports that AD predisposes to FA and not vice versa, while food allergens are presumed as one of the triggers of AD exacerbations. AD management should focus on skin care combined with topical and/or systemic treatments; however, in the presence of suspected food allergy, a thorough allergy evaluation should be performed. Food-elimination diets in food-allergic cases may have a beneficial effect on AD morbidity; however, prolonged, unnecessary diets are highly discouraged since they can lead to loss of tolerance and potentially increase the risk of IgE-mediated food allergy. Preventive AD strategies with the use of topical emollients and anti-inflammatory agents as well as early introduction of food allergens in high-risk infants seem promising in managing and preventing food allergy in AD patients. The current review aims to overview data on the complex AD/FA relationship and provide the most recent developments on whether food allergy interventions change the AD course and vice versa.
... Our skin microbiota is comprised of millions of microbial species including, bacteria, yeast, fungi, and viruses, and Growth factors Heparin-binding endothelial growth factor, Fibroblast growth factor, types 1, 2, and 4, Platelet-derived growth factor, Type-1 insulin-like growth factor Important in wound healing and damage repair by stimulating collagen/elastin production (Husein el Hadmed and Castillo 2016) (Alamgir 2017) maintaining the right balance between them is required for healthy skin (Byrd et al. 2018). Several skin disorders have been associated with alteration in microbial communities, such as atopic dermatitis with Staphylococcus aureus species (Kim et al. 2019), acne with Cutibacterium acnes, and Staphylococcus epidermidis (Fournière et al. 2020), dandruff with Malassezia species (Saxena et al. 2018), psoriasis with an increase in Firmicutes (Koper et al. 2020), etc. Some microbes modulate the body odor in particular auxiliary odor by decomposition of apocrine sweat and foot odors from eccrine sweat (James 2020). ...
Article
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The paper provides an overview of biocosmetics, which has tremendous potential for growth and is attracting huge business opportunities. It emphasizes the immediate need to replace conventional fossil-based ingredients in cosmetics with natural, safe, and effective ingredients. It assembles recent technologies viable in the production/extraction of the bioactive ingredient, product development, and formulation processes, its rapid and smooth delivery to the target site, and fosters bio-based cosmetic packaging. It further explores industries that can be a trailblazer in supplying raw material for extraction of bio-based ingredients for cosmetics, creating biodegradable packaging, or weaving innovation in fashion clothing. Lastly, the paper discusses what it takes to become the first generation of a circular economy and supports the implementation of strict regulatory guidelines for any cosmetic sold globally.
... 2,13 Esto condiciona el inicio de la respuesta inflamatoria a partir de la sensibilización del estrato córneo frente al agente externo, relacionado a su vez, con la sobreexpresión de células dendríticas. Posteriormente son activadas las células Th2 que intervienen en la producción de IL-4, IL-5 e IL-13, activación de células B que propicia el incremento de IgE y activación de mastocitos que estimula la liberación de mediadores de mastocitos (aminas y enzimas preformadas, especialmente histamina), lo cual produce prurito, rascado y ardor 13 . Las citocinas liberadas por las células T activadas y los mastocitos atraen en la piel a los granulocitos, especialmente eosinófilos, que contribuyen al daño celular 12 . ...
Article
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La dermatitis atópica constituye la enfermedad inflamatoria crónica más co-mún de la piel. La predisposición genética, la alteración de la barrera epidérmi-ca y la desregulación del sistema inmunológico son algunos de los componen-tes críticos de la dermatitis atópica. Una barrera cutánea deteriorada puede ser el paso inicial en el desarrollo de la marcha atópica, así como la inflamación de la piel mediada por el incremento de citocinas Th2, como la IL- 4, IL-5 e IL-13, contribuyen al desarrollo de la dermatitis atópica. Por otro lado, se ha de-mostrado que el estrés oxidativo juega un papel primordial en la fisiopatolo-gía de esta enfermedad. En este sentido el objetivo de este trabajo de revisión es demostrar la relación que existe entre la dermatitis atópica vinculada con la respuesta inflamatoria y el estrés oxidativo. Para ello se recopiló toda la infor-mación publicada que se encontró disponible en la base de datos de PubMed. Se realizó una descripción sobre la patogenia de la dermatitis atópica y su re-lación con el estrés oxidativo. Se concluye que la dermatitis atópica, como pro-ceso inflamatorio, desencadena mecanismos fisiopatológicos que involucran un estrés oxidativo.
... En revanche, peu d'études se sont intéressées au rôle des toxines PSMs dans l'inflammation cutanée et, notamment, dans l'exacerbation de l'inflammation dans la DA à l'origine de poussées. Pourtant, parmi les patients atteints de DA, 10 à 30 % sont colonisés par des souches potentiellement sécrétrices à haut niveau de PSMs car résistantes à la méticilline ou SARM [150,151]. En effet, il a été montré que les souches de SARM acquises dans la communauté, produisaient des PSMα en plus grande quantités que les souches sensibles à cet antibiotique. De plus, les PSMs ont été identifiées comme facteur majeur de la virulence de ces souches, en amplifiant leur activité cytolytique [167,382]. ...
Thesis
La dermatite atopique (DA) est une maladie chronique inflammatoire de la peau qui se caractérise par une altération de la barrière cutanée, une dysfonction dans la réponse immunitaire et une dysbiose du microbiote cutanée associée à une forte colonisation par Staphylococcus aureus. De plus, les patients atteints de DA ont un risque de développer des infections virales, notamment l’eczéma herpétique (EH) causé par le virus herpes simplex (HSV). Cependant, la physiopathologie de l’EH ainsi que le rôle des facteurs de virulence de S. aureus sont peu connus et le lien entre infections virales et bactériennes est non déterminé. Dans cette étude, nous nous sommes intéressés au rôle des toxines Phenol-Soluble Modulines (PSMs) de S. aureus en utilisant le PSMα3 synthétique et purifié et les sécrétomes de 3 souches de S. aureus, une qui exprime tous les PSMs, une délétée pour les PSMα et une délétée pour l’ensemble des PSMs. Nous avons ainsi mis en évidence, à la fois dans un modèle in vitro de kératinocytes primaires humains et ex vivo d’explants de peau, une induction de l’expression et de la production de médiateurs pro-inflammatoires par les PSMα à des concentrations non lytiques. En revanche, les PSMs de S. aureus ne semblent pas favoriser la réplication de l’HSV. D’autres part, nous étudions les interactions entre les cytokines pro-inflammatoires surexprimées dans la DA et les infections par HSV-1. Ainsi, nous avons mis en évidence, que dans un modèle 3D, trois combinaisons de cytokines surexprimées dans la DA favorisaient la réplication d’HSV-1 ce qui en fait donc des facteurs prédisposant à l’EH. Enfin, à ce jour, peu de traitements contre les infections par HSV existent et de nombreuses résistances à l’acyclovir, traitement le plus fréquent, apparaissent. Nous avons identifié deux cathélicidines, l’une issue du python birman (PB-Cath) et l’autre du rat taupe glabre (HG-Cath) comme de potentiels candidats puisqu’ils réduisent significativement la réplication d’HSV-1 dans des kératinocytes primaires humains.
... Как следствие, уменьшение общего количества церамидов обнаруживали у пациентов с АтД как в пораженных, так и в визуально здоровых участках кожи [11,12]. Большинство исследователей предполагают, что кожный микробиом также изменяется и находится под влиянием физической, окружаю щей и социальной среды, в которой находится пациент [13][14][15][16]. ...
Article
Introduction. Colonization of the skin with S. aureus and S. epidermidis in children with atopic dermatitis leads to the initiation of inflammation and worsening of the disease. The control of overcolonization with S. aureus is an important issue in pediatric dermatological practice. At the same time, to achieve a controlled level of colonization, it is preferable to prescribe non-steroidal external agents. Activated zinc pyrithione has a wide range of complementary pharmacodynamic effects, including anti-inflammatory, pro-apoptogenic, antimicrobial, and antifungal. The article presents the results of the use of zinc pyrithione in mild IgE-independent atopic dermatitis in children. The results of the main clinical studies confirming the effect of zinc pyrithione on the microbiome in AD and the severity of the disease were analyzed. Aim. To evaluate the therapeutic and microbiological efficacy of activated zinc pyrithione as monotherapy in patients with IgEindependent atopic dermatitis. Materials and methods. 30 patients aged 2 to 8 years with mild atopic dermatitis in the acute stage were divided into 2 groups. Group 1 received activated zinc pyrithione, group 2 received a combined topical steroid. Results. Both groups showed a significant reduction in S. aureus skin colonization. In both groups, in comparison with the initial state, a significant decrease in the severity of clinical manifestations of AD was obtained. The therapeutic efficacy of zinc pyrithione was 93.3%, clinical remission was observed in 73.3% of cases. Conclusion. The totality of currently available data on the clinical efficacy and safety of activated zinc pyrithione allows us to recommend it as one of the effective agents for external therapy of mild IgE-independent atopic dermatitis. The use of activated zinc pyrithione showed a rapid, pronounced positive result of treatment, a decrease in the risk of secondary infection in observed children with IgE-independent atopic dermatitis.
... Atopic dermatitis (a skin barrier dysfunction) tends to be associated with skin MRSA. [13][14][15] The reported salvage rate after MRSA infection is low. 6,12,16 Thus, for patients with poorly controlled atopic dermatitis in whom skin MRSA is present, rigorous preoperative skin care is needed, and skin cultures must be prepared. ...
Article
Objectives: Breast reconstruction using synthetic materials has increased rapidly in Japan since July 2013, when national health insurance began covering the procedure. Although synthetic material-based reconstruction of other body parts has not resulted in wounds with complications, this significant advantage is overshadowed by a risk of complications, including infection, following breast reconstruction. We therefore reviewed breast-reconstruction patients who experienced infection after implantation of synthetic materials and the countermeasures we used to address the problem. Methods: From July 2013 through December 2019, our department performed primary breast reconstructions using tissue expanders (TEs) in 106 patients and secondary breast reconstructions in 39 patients. We retrospectively reviewed these 145 patients in terms of their age, body mass index, timing of the reconstruction, presence/absence of both chemotherapy and radiation therapy before and after surgery, presence/absence of postoperative wound complications, and presence/absence of atopic dermatitis. We then evaluated whether these factors put patients at risk for postoperative TE infection. Results: Among the 145 patients who underwent reconstruction with TE, 3 (2.0%) were diagnosed with a postoperative TE infection. Our review revealed that necrosis of the skin around the surgical wound (P=0.004) and atopic dermatitis (P=0.041) were risk factors for TE infection. Conclusions: Infection following breast reconstruction with synthetic materials is a serious complication. Thus, patients requiring this surgery deserve optimal perioperative management. For those with known risk factors, a more appropriate surgical approach-e.g., using autologous tissue instead of a synthetic material-could be considered.
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Superantigens are unconventional antigens which recognise immune receptors outside their usual recognition sites e.g. complementary determining regions (CDRs), to elicit a response within the target cell. T-cell superantigens crosslink T-cell receptors and MHC Class II molecules on antigen-presenting cells, leading to lymphocyte recruitment, induction of cytokine storms and T-cell anergy or apoptosis among many other effects. B-cell superantigens, on the other hand, bind immunoglobulins on B-cells, affecting opsonisation, IgG-mediated phagocytosis, and driving apoptosis. Here, through a review of the structural basis for recognition of immune receptors by superantigens, we show that their binding interfaces share specific physicochemical characteristics when compared with other protein-protein interaction complexes. Given that antibody-binding superantigens have been exploited extensively in industrial antibody purification, these observations could facilitate further protein engineering to optimize the use of superantigens in this and other areas of biotechnology.
Article
Allergies are considered to represent mal-directed type 2 immune responses against mostly innocuous exogenous compounds. Immunoglobulin E (IgE) antibodies are a characteristic feature of allergies and mediate hypersensitivity against allergens through activation of effector cells, particularly mast cells (MCs). Although the physiological functions of this dangerous branch of immunity have remained enigmatic, recent evidence shows that allergic immune reactions can help to protect against the toxicity of venoms. Because bacteria are a potent alternative source of toxins, we assessed the possible role of allergy-like type 2 immunity in antibacterial host defense. We discovered that the adaptive immune response against Staphylococcus aureus (SA) skin infection substantially improved systemic host defense against secondary SA infections in mice. Moreover, this acquired protection depended on IgE effector mechanisms and MCs. Importantly, our results reveal a previously unknown physiological function of allergic immune responses, IgE antibodies, and MCs in host defense against a pathogenic bacterium.
Article
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We have previously reported on a novel nanoparticle formulation that was effective at killing Staphylococcus aureus in vitro. Here, we report for the first time, the antibacterial effects of a lipidic nano-carrier containing rifampicin (NanoRIF) which can be used to successfully treat Methicillin-Resistant S. aureus (MRSA) infection at a reduced antibiotic dosage compared to the free drug in a skin wound model in mice. The formulation used contains the lipid monoolein, a cationic lipid N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate (DOTAP) and the antibiotic. We have shown that rifampicin-loaded nanoparticles are more effective at treating infection in the skin wound model than the antibiotic alone. Cryo-TEM was used to capture for the first time, interactions of the formed nanoparticles with the cell wall of an individual bacterium. Our data strongly indicate enhanced binding of these charged nanoparticles with the negatively charged bacterial membrane. The efficacy we have now observed in vivo is of significant importance for the continued development of nanomedicine-based strategies to combat antibiotic resistant bacterial skin infections.
Article
The human microbiota has been established as a key regulator of host health, in large part due to its constant interaction with, and impact on, host immunity. A range of environmental exposures, spanning from the prenatal period through adulthood are now known to impact the composition and molecular productivity of microbiomes across mucosal and dermal tissues with short- and long-term consequences for host immune function. Here we review the more recent findings in the field that provide insights into how microbial-immune interactions promote and sustain immune dysfunction associated with allergy and asthma. We consider both early life microbiome perturbation and the molecular underpinnings of immune dysfunction associated with subsequent allergy and asthma development in childhood, as well as microbiome features that relate to phenotypic attributes of allergy and asthma in older patients with established disease.
Thesis
La dermatite atopique (DA) est une maladie cutanée inflammatoire fréquente. Le prurit est présent chez presque tous les patients et a un impact négatif sur la qualité de vie des personnes touchées et de leur famille. Bien que plusieurs modèles tridimensionnels in vitro imitant la DA soient publiés, aucun ne prend en compte l'inflammation neurogène et le prurit. L'objectif était de développer un modèle humain d’explant cutané réinnervé dans le contexte inflammatoire Th2 de la DA. Les explants de peau humaine étaient réinnervés par des neurones sensoriels primaires dérivés du ganglion de la racine dorsale (DRG) de rats. Le modèle était traité ou non avec un cocktail inflammatoire (interleukine-4/-13, facteur de nécrose tumorale-α et acide polyinosinique - polycytidylique). Dans un deuxième temps, les neurones sensoriels dérivés des SKPs étaient analysés afin d'évaluer leurs capacités à remplacer les neurones issus des DRG. Les explants étaient réinnervés après 5 jours de co-culture. L'inflammation reproduisait les caractéristiques de la DA au niveau de l’explant cutané. Mais après réinnervation, les marqueurs d'inflammation n'étaient pas augmentés. En ce qui concerne la barrière épidermique, l'expression de la filaggrine n'était pas diminuée dans le contexte inflammatoire après la réinnervation. Les fibres nerveuses protègeaient les kératinocytes et empêchaient l'inflammation et les anomalies de la barrière épidermique. L'absence d'inflammation neurogène secondaire à l'ajout du cocktail inflammatoire semble être due à la nature hétérologue du modèle. Pour surmonter ce biais, nous avons caractérisé les neurones sensoriels dérivés des SKP. Ces SKP présentent les différents marqueurs de la voie de signalisation du prurit de la DA et sont capables de sécréter des neuropeptides. La prochaine étape consiste à confirmer leur capacité à réinventer un explant de peau puis d’ajouter le cocktail inflammatoire et évaluer la présence ou non d’une inflammation neurogène.
Article
Atopic dermatitis (AD) is a common inflammatory skin disease, with a prevalence of up to 20% in children with wide regional variability.¹ Affected patients are at risk of developing a variety of viral and bacterial infections.² Disseminated viral infections, such as eczema herpeticatum, eczema vaccinatum, eczema molluscatum, or eczema coxsackium are named after their causative virus and have been frequently reported in AD patients.
Article
The dysregulation of skin microflora in patients with atopic dermatitis (AD) has become a research hotspot in recent years. Metagenomic studies have shown that microbial diversity is decreased, whereas the Staphylococcus aureus infection is increased in AD. Keratinocytes are the primary barrier against the invasion of external pathogenic microorganisms. Staphylococcus aureus infection can abnormally activate innate and adaptive immune responses in keratinocytes, resulting in a vicious cycle between Staphylococcus aureus infection and AD. This article reviews the mechanisms of inflammatory damage of keratinocytes induced by Staphylococcus aureus infection in patients with AD, providing a theoretical basis for the study of new targeted drugs. This review also suggests for the management of Staphylococcus aureus infection in patients with AD. Review of the mechanisms underlying the immune and inflammatory damage from keratinocytes caused by S. aureus; may help guide treatment options for patients with atopic dermatitis.
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Purpose: Evidence supporting a link between indoor formaldehyde exposure and atopic dermatitis (AD) in humans is limited. The purpose of this longitudinal study was to investigate whether AD symptoms in children could be affected by indoor formaldehyde levels in ordinary households. Methods: Fifty-five children with moderate-to-severe AD aged under 18 years were enrolled as a panel. They were followed up from February 2019 through February 2020. Indoor formaldehyde levels of patients' houses and their AD symptoms were repeatedly measured on a daily basis. The generalized linear mixed model was utilized for statistical analysis. Subdivision analysis was performed by stratifying patients by sex, body mass index, presence of parental allergy, and indoor environments including mold/dampness, temperature, and relative humidity (RH). Results: A total of 4,789 person-days of AD symptom data were collected. The average concentration of formaldehyde was 13.6 ± 16.4 ppb, with the highest value found in spring (18.1 ± 20.6 ppb). Higher levels of formaldehyde were observed when there was parental smoking, increased indoor temperature over 25.5°C, or RH over 60% (P < 0.0001). When the effect size was compared between each season after controlling for ambient particulate matter, temperature, and RH, an increase in 10 ppb of formaldehyde increased AD symptoms by 79.2% (95% confidence interval [CI], 19.6-168.4) in spring and by 39.9% (95% CI, 14.3-71.2) in summer. AD symptoms in children aged 6-18 years appeared to increase significantly, whereas there was no significant increase in children under 6 years. When indoor temperature was over 25.5°C, an increase in formaldehyde by 10 ppb increased AD symptoms by 17.8% (95% CI, 3.9-33.6). Conclusions: Indoor formaldehyde can exacerbate AD symptom in children with moderate-to-severe AD, particularly in spring and summer, even at allowable levels. Thus, minimizing exposure to indoor formaldehyde may be needed for the proper management of AD in children.
Article
A strong association has been established between Staphylococcus aureus and atopic dermatitis (AD). Although the exact mechanism of this relationship remains unclear, many studies have characterized differences in S. aureus between individuals with AD and unaffected controls. Patients with AD have higher cutaneous colonization with S. aureus, with increased bacterial density correlating with AD severity. S. aureus virulence factors can exacerbate the immune dysregulation seen in AD. Consequently, AD treatments have shifted to focus on S. aureus as a therapeutic target, including skin bacterial transplant and probiotics. In addition, traditional mainstays of AD treatment, such as corticosteroids, have been found to induce changes in the cutaneous microbiota and S. aureus levels, underscoring its importance in the pathogenesis of AD. Nonpharmacological treatments have been investigated as well, without definitive results. Both bacteriotherapy and nonpharmacological treatments merit continued study on their effects on S. aureus colonization and role in the treatment of AD.
Chapter
Allergens, in addition to others, are important aggravating factors for atopic dermatitis (AD), and causative allergens can differ with age in AD patients. For young children, food allergens, such as peanut, egg, and milk, are important, and sensitization to food allergens in pediatric AD patients has been recognized as an important biomarker of progression to respiratory allergic disease, known as allergy march. For adult AD patients, inhalant allergens, such as house dust mite, pet dander, and pollens, are important, and positive randomized clinical trials of immunotherapy or avoidance treatments have supported a causal relationship between allergen and AD. Dysbiosis and decreased diversity in microorganisms are also cardinal features of AD. Expansions of Staphylococcus aureus with or without methicillin resistance, Candida albicans, and Malassezia colonization are usually found, along with fewer commensal microorganisms, in AD patients. These microorganisms produce endotoxins, proteases, and other virulent proteins that induce skin barrier dysfunction and also act as important aggravating factors of Th2 inflammation. Interestingly, AD patients exhibit sIgE to enterotoxins of Staphylococcus aureus and proteins of Malassezia and other fungi, suggesting that some microorganism products act as allergens and activate mast cells and basophils, leading to the release of preformed mediators, leukotrienes, and cytokines. In summary, sensitization to food, inhalant, and microorganisms plays a cardinal role in the pathogenesis and aggravation of AD and may also contribute to allergy march. Clinicians should keep in mind that identification of culprit allergens, followed by avoidance and immune immunotherapy, is crucial to the management of AD patients.
Article
Background: Glabridin (GB), a bio-available phytoestrogen, displays various biological properties such as anti-inflammatory, antibacterial, and antiviral. Objective: To explore the role of GB in the process of atopic dermatitis (AD). Methods: CCK8 was used to detect the therapeutic effect of Glabridin in HaCat and NHEK cell inflammatory models. And evaluated the effect on cell proliferation and cell viability. The expression of TLR4, MyD88, P65 and P50 in HaCat and NHEK cell tissues was detected by qRT-PCR and PCR. At the same time, an AD animal model was constructed, and the cell experiment results were verified by hematoxylin-eosin (HE) and Immunohistochemistry staining (IHC). Results: Enzyme-linked immunosorbent assay (ELISA) demonstrated that IL-1β, IL-6, and TNF-α upregulated by lipopolysaccharide (LPS) was decreased by treatment with GB. AD progression was further confirmed to be regulated by GB by inhibiting the TLR4/MyD88/NF-κB signaling pathway through real-time PCR and Western blot analyses. An AD-like mouse model demonstrated that GB considerably alleviated epidermal injury, relieve edema, and reduced inflammatory cell infiltration by H&E staining. Concurrently, IHC staining exhibited GB to reduce AD progression by impeding TLR4 expression. Conclusion: GB was observed to decrease the AD progression by suppressing the TLR4/MyD88/NF-κB signaling pathway, which may likely serve as a novel therapeutic drug for AD management.
Article
Background Our skin is a very important and complex organ of the body. The microorganisms of the skin, the so-called microbiome, represent an important part of the healthy skin barrier and are influenced by various external and internal factors.AimThe question to what extent the skin microbiome represents a diagnostic or even therapeutic target in the context of skin diseases is discussed.Materials and methodsA literature search was performed.ResultsSeveral diseases are associated with negative alterations of the skin microbiome. In atopic dermatitis, a correlation between severity and increased availability of Staphylococcus aureus is known, with a loss of bacterial diversity on the skin. In the future, S. aureus will not only be used as a diagnostic marker in atopic dermatitis, but also represents a promising target as a predictive marker for therapeutic success. The role of the skin microbiome in psoriasis has not yet been researched in depth. However, there is evidence that dysbiosis of the skin microbiome contributes to the course of psoriasis and that there is a disturbance in immune tolerance in patients. In the case of acne, the involvement of Cutibacterium acnes in the clinical picture is well known; however, recent findings show that it is not sufficient to identify the species, but certain characteristics of C. acnes strains are associated.Conclusion Microbial biomarkers are currently only established in atopic dermatitis. For other diseases, this might be the case in the future; however combinations of microorganisms, single species and also strains with specific characteristics must be considered.
Article
Skin is an organ with a dynamic ecosystem that harbors pathogenic and commensal microbes, which constantly communicate amongst each other and with the host immune system. Evolutionarily, skin and its microbiota have evolved to remain in homeostasis. However, frequently this homeostatic relationship is disturbed by a variety of factors such as environmental stress, diet, genetic mutations, and the microbiome itself. Commensal microbes also play a major role in the maintenance of microbial homeostasis. In addition to their ability to limit pathogens, many skin commensals such as Staphylococcus epidermidis and Cutibacterium acnes have recently been implicated in disease pathogenesis either by directly modulating the host immune components or by supporting the expansion of other pathogenic microbes. Likewise, opportunistic skin pathogens such as Staphylococcus aureus and Staphylococcus lugdunensis are able to breach the skin and cause disease. Though much has been established about the microbiota’s function in skin immunity, we are in a time where newer mechanistic insights rapidly redefine our understanding of the host/microbial interface in the skin. In this review, we provide a concise summary of recent advances in our understanding of the interplay between host defense strategies and the skin microbiota.
Article
Background and Objectives Glabridin is usually used to treat cardiovascular and central nervous system diseases, which is a main bioactive phytoconstituent of licorice root. In this study, our aim was to obtain metabolic profiles of glabridin in rat plasma, urine, bile, and feces after intragastric and intravenous administration.Methods By UPLC–QTOF–MS, the metabolites of glabridin were systematically analyzed and identified. An ACQUITY UPLC HSS T3 column (100 × 2.1 mm, 1.8 mm) and the mobile phase containing water with 0.1% formic acid (A) and acetonitrile with 0.1% formic acid (B) via gradient elution was used as the chromatographic condition for separation. An extracted ion chromatogram strategy with multiple prototype/metabolite intermediate templates and 71 typical metabolic reactions was suggested to completely profile the metabolites of glabridin.ResultsFor the first time, 13 compounds in total were recognized from urine, plasma, bile, and feces of rats with the metabolite profiling strategy. The main metabolic form of glabridin in rats consisted of the prototype, hydroxylation, glucuronide conjugation, decarbonylation, and tert-butyl to alcohol metabolites.Conclusions The results not only indicated a comprehensive study on the probable metabolic pathways of glabridin in vivo, but also provided useful data and information for future pharmacological studies of glabridin.
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Skin barrier dysfunction has been reported in both atopic dermatitis (AD) and food allergy (FA). However, only one-third of patients with AD have FA. The purpose of this study was to use a minimally invasive skin tape strip sampling method and a multiomics approach to determine whether children with AD and FA (AD FA +) have stratum corneum (SC) abnormalities that distinguish them from AD without FA (AD FA −) and nonatopic (NA) controls. Transepidermal water loss was found to be increased in AD FA +. Filaggrin and the proportion of ω-hydroxy fatty acid sphingosine ceramide content in nonlesional skin of children with AD FA + were substantially lower than in AD FA − and NA skin. These abnormalities correlated with morphologic changes in epidermal lamellar bilayer architecture responsible for barrier homeostasis. Shotgun metagenomic studies revealed that the nonlesional skin of AD FA + had increased abundance of Staphylococcus aureus compared to NA. Increased expression of keratins 5, 14, and 16 indicative of hyperproliferative keratinocytes was observed in the SC of AD FA +. The skin transcriptome of AD FA + had increased gene expression for dendritic cells and type 2 immune pathways. A network analysis revealed keratins 5, 14, and 16 were positively correlated with AD FA +, whereas filaggrin breakdown products were negatively correlated with AD FA +. These data suggest that the most superficial compartment of nonlesional skin in AD FA + has unique properties associated with an immature skin barrier and type 2 immune activation.
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The Atopic march denotes the progression from atopic dermatitis (AD) to the development of other allergic disorders such as immunoglobulin (Ig) E-mediated food allergy, allergic rhinitis and asthma in later childhood. There is increasing evidence from prospective birth cohort studies that early-onset AD is a risk factor for other allergic diseases or is found in strong association with them. Animal studies now provide mechanistic insights into the pathways that may be responsible for triggering the progression from the skin barrier dysfunction seen in AD to epicutaneous sensitization, food allergy and allergic airway disorders. Recent large randomized controlled trials have demonstrated the efficacy of early interventions targeted at AD and food allergy prevention. These show great promise for research into future strategies aimed at prevention of the atopic march.
Article
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As an interface with the environment, the skin is a complex ecosystem colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome inhibits colonization with pathogens, such as Staphylococcus aureus, and is a crucial component for function of the epidermal barrier. Moreover, crosstalk between commensals and the immune system is now recognized because microorganisms can modulate both innate and adaptive immune responses. Host-commensal interactions also have an effect on the developing immune system in infants and, subsequently, the occurrence of diseases, such as asthma and atopic dermatitis (AD). Later in life, the cutaneous microbiome contributes to the development and course of skin disease. Accordingly, in patients with AD, a decrease in microbiome diversity correlates with disease severity and increased colonization with pathogenic bacteria, such as S aureus. Early clinical studies suggest that topical application of commensal organisms (eg, Staphylococcus hominis or Roseomonas mucosa) reduces AD severity, which supports an important role for commensals in decreasing S aureus colonization in patients with AD. Advancing knowledge of the cutaneous microbiome and its function in modulating the course of skin disorders, such as AD, might result in novel therapeutic strategies.
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The bacterial pathogen Staphylococcus aureus plays an important role in atopic dermatitis (AD), a chronic disorder that mostly affects children. Colonization of the skin of AD patients by S. aureus exacerbates the disease, but the molecular determinants of the bacterium-skin adhesive interactions are poorly understood. Specifically, reduced levels of natural moisturizing factor (NMF) in the stratum corneum have been shown to be associated with more severe AD symptoms, but whether this is directly related to S. aureus adhesion is still an open question. Here, we demonstrate a novel relationship between NMF expression in AD skin and strength of bacterial adhesion. Low-NMF corneocytes, unlike high-NMF ones, are covered by a dense layer of nanoscale villus protrusions. S. aureus bacteria isolated from AD skin bind much more strongly to corneocytes when the NMF level is reduced. Strong binding forces originate from a specific interaction between the bacterial adhesion clumping factor B (ClfB) and skin ligands. Remarkably, mechanical tension dramatically strengthens ClfB-mediated adhesion, as observed with catch bonds, demonstrating that physical stress plays a role in promoting colonization of AD skin by S. aureus. Collectively, our findings demonstrate that patient NMF levels regulate the strength of S. aureus-corneocyte adhesion, the first step in skin colonization, and suggest that the ClfB binding mechanism could represent a potential target for new therapeutic treatments.
Article
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The epidermis contains epithelial cells, immune cells, and microbes which provides a physical and functional barrier to the protection of human skin. It plays critical roles in preventing environmental allergen penetration into the human body and responsing to microbial pathogens. Atopic dermatitis (AD) is the most common, complex chronic inflammatory skin disease. Skin barrier dysfunction is the initial step in the development of AD. Multiple factors, including immune dysregulation, filaggrin mutations, deficiency of antimicrobial peptides, and skin dysbiosis contribute to skin barrier defects. In the initial phase of AD, treatment with moisturizers improves skin barrier function and prevents the development of AD. With the progression of AD, effective topical and systemic therapies are needed to reduce immune pathway activation and general inflammation. Targeted microbiome therapy is also being developed to correct skin dysbiosis associated with AD. Improved identification and characterization of AD phenotypes and endotypes are required to optimize the precision medicine approach to AD. © Copyright The Korean Academy of Asthma, Allergy and Clinical Immunology.
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Staphylococcus aureus plays an important role in skin and soft tissue infections and contributes to the pathophysiology of complex skin disorders such as atopic dermatitis. Bacterial resistance against commonly used antibiotics has increased considerably in the last decades demanding alternative treatment approaches. We present 3 cases where patients with chronic and recurrent S. aureus-related dermatoses were successfully treated with Staphefekt SA.100. Staphefekt SA.100 is a recombinant phage endolysin for topical skin application that specifically targets both methicillin-sensitive and methicillin-resistant S. aureus. As a consequence of its specific mechanism of action, bacterial resistance is unlikely to develop. In our 3 cases, resistance induction was not observed. Our results indicate that targeted treatment with Staphefekt might be an attractive alternative for (long-term) classical antibiotic therapy, and confirmatory randomized controlled trials are warranted to evaluate its clinical efficacy and safety.
Article
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Staphylococcus aureus skin infection is a frequent and recurrent problem in children with the common inflammatory skin disease atopic dermatitis (AD). S. aureus colonises the skin of the majority of children with AD and exacerbates the disease. The first step during colonisation and infection is bacterial adhesion to the cornified envelope of corneocytes in the outer layer stratum corneum. Corneocytes from AD skin are structurally different to corneocytes from normal healthy skin. The objective of this study was to identify bacterial proteins that promote the adherence of S. aureus to AD corneocytes. S. aureus strains from clonal complex 1 and 8 were more frequently isolated from infected AD skin than from the nasal cavity of healthy children. AD strains had increased ClfB ligand binding activity compared to normal nasal carriage strains. Adherence of single S. aureus bacteria to corneocytes from AD patients ex vivo was studied using atomic force microscopy. Bacteria expressing ClfB recognised ligands distributed over the entire corneocyte surface. The ability of an isogenic ClfB-deficient mutant to adhere to AD corneocytes was greatly reduced compared to its parent clonal complex 1 clinical strain. ClfB from clonal complex 1 strains had a slightly higher binding affinity for its ligand compared to ClfB from other clonal complexes. Our results provide new insights into the first step in the establishment of S. aureus colonisation in AD patients. ClfB is a key adhesion molecule for the interaction of S.aureus with AD corneocytes and represents a target for intervention.
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Background: Atopic dermatitis (AD) is a prevalent disease with significant impact on physical health and quality of life. Staphylococcus aureus (S. aureus) has been directly correlated to disease severity, and may also be a contributing causal factor in the pathogenesis of AD. The primary aim of the present study was to assess differences in S. aureus colonization in AD patients with and without filaggrin gene (FLG) mutations. Secondarily, to assess disease severity in relation to S. aureus colonization. Exploratory analyses were performed to investigate S. aureus genetic lineages in relation to FLG mutations and disease severity (SCORAD). Methods: 101 adult AD patients were included in the study. Bacterial swabs were taken from lesional skin, non-lesional skin and nose. Swabs positive for S. aureus were characterized by spa and the respective clonal complex (CC) type assigned. Patients were characterized with respect to disease severity (SCORAD) and FLG mutations (n=88). Fischer's exact test was used to analyze differences in S. aureus colonization in relation to FLG mutations. Results: Of the 101 patients included, 74 patients (73%) were colonized with S. aureus. Of the colonized patients, 70 patients (95%) carried only one CC type in all three different sampling sites. In lesional skin S. aureus was found in 24 patients with FLG mutations (n=31), versus 24 wild-type patients (n=54) (p=0.0004). S. aureus CC1 clonal lineage was more prevalent in patients with FLG mutations (n=10) than in wild-type patients (n=2) (p=0.003). No specific bacterial lineage was linked to disease severity. Conclusion: Increased S. aureus colonization in AD patients with FLG mutations, and increased prevalence of CC1 in patients with FLG mutations, suggest that host-microbe interactions and clonal differences in S. aureus are important for colonization of AD skin. This article is protected by copyright. All rights reserved.
Article
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The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing Staphylococcus aureus, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against S. aureus was performed on isolates of coagulase-negative Staphylococcus (CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by S. aureus. The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including Staphylococcus epidermidis and Staphylococcus hominis. These AMPs were strain-specific, highly potent, selectively killed S. aureus, and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by S. aureus. These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease.
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Atopic dermatitis (AD) is a common allergic skin disease that is associated with chronic, recurrent eczematous and pruritic lesions at the flexural folds caused by interacting factors related to environmental and immune system changes. AD results in dry skin, and immunoglobulin E-mediated allergic reactions to foods and environmental allergens. While steroids and anti-histamines temporarily relieve the symptoms of AD, the possibility of side effects from pharmacological interventions remains. Despite intensive research, the underlying mechanisms for AD have not been clarified. A study of Staphylococcus aureus (S. aureus) established the role of its toxins in the pathogenesis of AD. Approximately 90% of patients with AD experience S. aureus colonization and up to 50%–60% of the colonizing S. aureus is toxin-producing. Any damage to the protective skin barrier allows for the entry of invading allergens and pathogens that further drive the pathogenesis of AD. Some natural toxins (or their components) that have therapeutic effects on AD have been studied. In addition, recent studies on inflammasomes as one component of the innate immune system have been carried out. Additionally, studies on the close relationship between the activation of inflammasomes and toxins in AD have been reported. This review highlights the literature that discusses the pathogenesis of AD, the role of toxins in AD, and the positive and negative effects of toxins on AD. Lastly, suggestions are made regarding the role of inflammasomes in AD.
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Background: Disease flares of established atopic dermatitis (AD) are generally associated with a low-diversity skin microbiota and Staphylococcus aureus dominance. The temporal transition of the skin microbiome between early infancy and the dysbiosis of established AD is unknown. Methods: We randomly selected 50 children from the Cork BASELINE longitudinal birth cohort for microbiome sampling at three times in the first six months of life, at four skin sites relevant to AD: the antecubital and popliteal fossae, nasal tip, and cheek. We identified ten infants who developed AD and compared them with ten randomly selected control infants with no AD. We performed bacterial 16S ribosomal RNA sequencing and analysis directly from clinical samples. Results: Bacterial community structures and diversity shifted over time, suggesting that age strongly affects the skin microbiome in infants. Unlike established AD, these infantile AD patients did not have noticeably dysbiotic communities prior to or with disease and were not colonized by S. aureus. In comparing patients and controls, infants who had affected skin at month 12 had statistically significant differences in bacterial communities on the antecubital fossa at month 2 compared to infants who were unaffected at month 12. In particular, commensal staphylococci were significantly less abundant in infants affected at month 12, suggesting that this genus may protect against the later development of AD. Conclusions: This study suggests that 12-month-old infants with AD were not colonized with Staphylococcus aureus before developing AD. Additional studies are needed to confirm if colonization with commensal staphylococci modulates skin immunity and attenuates development of AD.
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Background: A small subset of adolescents atopic dermatitis (AD) tends to persist. This also leads to get more antibiotics exposure with advancing years. Antibiotic resistance has been regarded as a serious problem during Staphylococcus aureus treatment, especially methicillin-resistant S. aureus (MRSA). Objective: It was investigated the S. aureus colonization frequency in the skin lesions and anterior nares of adolescent AD patients and evaluated the changes in S. aureus antimicrobial susceptibility for years. Methods: Patients who visited our clinic from September 2003 to August 2005 were classified into group A, and patients who visited from August 2010 to March 2012 were classified into group B. To investigate the differences with regard to patients' age and disease duration, the patients were subdivided into groups according to age. Lesional and nasal specimens were examined. Results: Among the 295 AD patients, the total S. aureus colonization rate in skin lesions was 66.9% (95/142) for group A and 78.4% (120/153) for group B. No significant changes in the systemic antimicrobial susceptibilities of S. aureus strains isolated from adolescent AD patients were observed during about 10-year period. The increased trend of MRSA isolation in recent adolescent AD outpatients suggest that the community including school could be the source of S. aureus antibiotic resistance and higher fusidic acid resistance rates provides evidence of imprudent topical use. Conclusion: Relatively high MRSA isolation and fusidic acid resistance rates in recent AD patients suggest that the community harbors antibiotic-resistant S. aureus.
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Atopic dermatitis (AD) is the most common allergic skin disease in the general population. It is a chronic inflammatory skin disease complicated by recurrent bacterial and viral infections that, when left untreated, can lead to significant complications. The current article will review immunologic and molecular mechanisms underlying the propensity of AD patients to microbial infections. These infections include Staphylococcus aureus (S. aureus) skin infections, eczema herpeticum, eczema vaccinatum, and eczema coxsackium. Previous studies have shown that skin barrier defects, a decrease in antimicrobial peptides, increased skin pH, or Th2 cytokines such as IL-4 and IL-13 are potential contributing factors for the increased risk of skin infections in AD. In addition, bacterial virulence such as methicillin-resistant S. aureus (MRSA) produces significantly higher number of superantigens that increase their potential in causing infection and more severe cutaneous inflammation in AD patients. More recent studies suggest that skin microbiome including Staphylococcus epidermidis or other coagulase-negative staphylococci may play an important role in controlling S. aureus skin infections in AD. Other studies also suggest that genetic variants in the innate immune response may predispose AD patients to increased risk of viral skin infections. These genetic variants include thymic stromal lymphopoietin (TSLP), type I interferon (α, ß, ω), type II interferon (γ), and molecular pathways that lead to the production of interferons (interferon regulatory factor 2). A common staphylococcal toxin, α-toxin, may also play a role in enhancing herpes simplex virus skin infections in AD. Further understanding of these disease processes may have important clinical implications for the prevention and treatment of skin infections in this common skin disease.
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Staphylococcus aureus is a well-known microbe that colonizes or infects the skin in atopic dermatitis (AD). The prevalence of methicillin-resistant S. aureus (MRSA) in AD has recently been increasing. This study aimed to determine the antimicrobial susceptibility patterns in AD skin lesions and evaluate the prevalence of MRSA in Korea. We also recommend proper first-line topical antibiotics for Korean patients with AD. We studied S. aureus-positive skin swabs (n=583) from the lesional skin of infants, children, and adults who presented to our outpatient clinic with AD from July 2009 to April 2012. S. aureus exhibited high susceptibility against most antimicrobial agents. However, it exhibited less susceptibility to benzylpenicillin, erythromycin, clindamycin, and fusidic acid. The prevalence of MRSA was 12.9% among 583 S. aureus isolates, and the susceptibility to oxacillin was significantly lower in infants in both acute and chronic AD lesions. S. aureus from AD has a high prevalence of MRSA and multidrug resistance, especially in infants. In addition, the rate of fusidic acid resistance is high among all age groups, and mupirocin resistance increases with age group regardless of lesional status. This is the first study comparing the antimicrobial susceptibility rates of S. aureus isolates from AD cases with respect to age and lesion status in Korea.
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Staphylococcus aureus is a human commensal that colonizes the skin. While it is normally innocuous, it has strong associations with atopic dermatitis pathogenesis, and has become the leading cause of skin and soft tissue infections in the USA. The factors that dictate the role of S. aureus in disease are still being determined. In this work, we utilized primary keratinocyte culture and an epidermal murine colonization model to investigate the role of S. aureus phenol soluble modulins (PSMs) on pro-inflammatory cytokine release and inflammation induction. We demonstrated that many species of Staphylococcus are capable of causing release of IL-18 from keratinocytes and that S. aureus PSMs are necessary and sufficient to stimulate IL-18 release from keratinocytes independent of caspase-1. Further, after seven days of epicutaneous exposure to wild type S. aureus, but not Δpsm S. aureus, we saw dramatic changes in gross pathology as well as systemic release of pro-inflammatory cytokines. This work demonstrates the importance of PSM peptides in S. aureus-mediated inflammatory cytokine release from keratinocytes in vitro and in vivo and further implicates PSMs as important contributors to pathogenesis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
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Understanding the Maxam-Gilbert and Sanger sequencing as the first generation, in recent years there has been an explosion of newly-developed sequencing strategies, which are usually referred to as next generation sequencing (NGS) techniques. NGS techniques have high-throughputs and produce thousands or even millions of sequences at the same time. These sequences allow for the accurate identification of microbial taxa, including uncultivable organisms and those present in small numbers. In specific applications, NGS provides a complete inventory of all microbial operons and genes present or being expressed under different study conditions. NGS techniques are revolutionizing the field of microbial ecology and have recently been used to examine several food ecosystems. After a short introduction to the most common NGS systems and platforms, this review addresses how NGS techniques have been employed in the study of food microbiota and food fermentations, and discusses their limits and perspectives. The most important findings are reviewed, including those made in the study of the microbiota of milk, fermented dairy products, and plant-, meat- and fishderived fermented foods. The knowledge that can be gained on microbial diversity, population structure and population dynamics via the use of these technologies could be vital in improving the monitoring and manipulation of foods and fermented food products. They should also improve their safety.
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Background: Colonization by methicillin-resistant Staphylococcus aureus (MRSA) in atopic dermatitis is little studied but has therapeutic implications. It may have a role in disease severity given the additional virulence factors associated. Aims: Our aims were to record the proportion of patients with MRSA colonization in atopic dermatitis and to ascertain if any association exists between MRSA colonization and disease severity. Methods: An observational cross-sectional study involving children aged≤12 years with atopic dermatitis attending the outpatient department of Government Medical College, Kottayam was conducted. Socio-demographic data, exacerbating factors and risk factors for hospital care-associated MRSA were documented. Extent of atopic dermatitis was recorded using a standardized scale (Eczema Area Severity Index, EASI). Skin swabs were taken from anterior nares and the worst affected atopic dermatitis sites for culture and sensitivity. Results: Of the 119 subjects recruited during the study period (November 2009-April 2011), Staphylococcus aureus was isolated from 110 (92.4%) patients and MRSA from 30 (25.21%) patients. A total of 18 patients with MRSA had risk factors for healthcare associated-MRSA. The patients whose cultures grew MRSA were found to have significantly higher EASI score when compared to those patients colonized with methicillin sensitive Staphylococcus aureus (P < 0.01). Presence of Staphylococcus aureus, early age of onset, presence of food allergies, seasonal exacerbation and inadequate breastfeeding did not seem to influence disease severity. Conclusions: There is a high degree of prevalence of MRSA (25.2%) in atopic dermatitis and presence of MRSA is associated with increased disease severity. Further studies are needed to validate these findings.
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Staphylococcus aureus (SA) has peculiar abilities to colonize the skin in atopic dermatitis (AD) patients. We sought to determine the colonization rates of SA in acute and chronic skin lesions of AD patients, to find any difference in colonization rates according to age and to find the influences of total immunoglobulin E (IgE) and eosinophil counts to the colonization of SA. We evaluated the total IgE level and eosinophil counts, and cultured SA from the skin lesions of 687 AD patients (131 acute and 556 chronic skin lesions) and 247 control urticaria patients (July 2009 to November 2010; Samsung Medical Center Dermatology Clinic, Seoul, Korea). The SA colonization rates were 74%, 38% and 3% in acute, chronic skin lesions and control skin, respectively, and they were increased with age in AD patients. The colonization rate in chronic skin lesions was higher in the high IgE/eosinophilia groups as compared to the normal IgE/eosinophil groups. The SA colonization rate was higher in AD patients and especially in acute lesions, and had a tendency to increase with age. As the colonization rates were only higher in the high IgE/eosinophilia groups of chronic skin lesions, we suggested that SA may invade the skin through barrier defects in acute skin lesions, but the colonization in chronic lesions may be orchestrated through many different factors.
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Atopic dermatitis is a chronic inflammatory skin disease that affects 15-30% of children and approximately 5% of adults in industrialized countries. Although the pathogenesis of atopic dermatitis is not fully understood, the disease is mediated by an abnormal immunoglobulin-E immune response in the setting of skin barrier dysfunction. Mast cells contribute to immunoglobulin-E-mediated allergic disorders including atopic dermatitis. Upon activation, mast cells release their membrane-bound cytosolic granules leading to the release of several molecules that are important in the pathogenesis of atopic dermatitis and host defence. More than 90% of patients with atopic dermatitis are colonized with Staphylococcus aureus in the lesional skin whereas most healthy individuals do not harbour the pathogen. Several staphylococcal exotoxins can act as superantigens and/or antigens in models of atopic dermatitis. However, the role of these staphylococcal exotoxins in disease pathogenesis remains unclear. Here we report that culture supernatants of S. aureus contain potent mast-cell degranulation activity. Biochemical analysis identified δ-toxin as the mast cell degranulation-inducing factor produced by S. aureus. Mast cell degranulation induced by δ-toxin depended on phosphoinositide 3-kinase and calcium (Ca(2+)) influx; however, unlike that mediated by immunoglobulin-E crosslinking, it did not require the spleen tyrosine kinase. In addition, immunoglobulin-E enhanced δ-toxin-induced mast cell degranulation in the absence of antigen. Furthermore, S. aureus isolates recovered from patients with atopic dermatitis produced large amounts of δ-toxin. Skin colonization with S. aureus, but not a mutant deficient in δ-toxin, promoted immunoglobulin-E and interleukin-4 production, as well as inflammatory skin disease. Furthermore, enhancement of immunoglobulin-E production and dermatitis by δ-toxin was abrogated in Kit(W-sh/W-sh) mast-cell-deficient mice and restored by mast cell reconstitution. These studies identify δ-toxin as a potent inducer of mast cell degranulation and suggest a mechanistic link between S. aureus colonization and allergic skin disease.
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SUMMARY This review begins with a discussion of the large family of Staphylococcus aureus and beta-hemolytic streptococcal pyrogenic toxin T lymphocyte superantigens from structural and immunobiological perspectives. With this as background, the review then discusses the major known and possible human disease associations with superantigens, including associations with toxic shock syndromes, atopic dermatitis, pneumonia, infective endocarditis, and autoimmune sequelae to streptococcal illnesses. Finally, the review addresses current and possible novel strategies to prevent superantigen production and passive and active immunization strategies.
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Atopic dermatitis (AD) is the initial step of the atopic march: the progression from AD to allergic rhinitis and asthma. There is a close association between skin barrier abnormalities and the development of AD and the atopic march. One of cardinal features of AD is that the lesional skin of the majority of AD patients is chronically colonized with Staphylococcus aureus with half isolates producing superantigen enterotoxin B (SEB). Although diverse roles of SEB in the pathogenesis and severity of AD have been recognized, whether SEB contributes to the dermal inflammation that drives lung inflammation and airway hyperresponsiveness (AHR) has not been examined. Here we show a novel role of S. aureus superantigen SEB in augmenting allergen ovalbumin (Ova) induced atopic march through an IL-17A dependent mechanism. When mice epicutaneously (EC) sensitized with allergen Ova, addition of topical SEB led to not only augmented systemic Th2 responses but also a markedly exaggerated systemic Th17/IL-17 immune environment. The ability of SEB in enhancing Th17/IL-17 was mediated through stimulating lymphocytes in spleen and draining lymph nodes to promote IL-6 production. Epicutaneous sensitization of mice with a combination of Ova and SEB significantly enhanced Ova-induced AHR and granulocytic lung inflammation than Ova allergen alone. When IL-17A was deleted genetically, the effects of SEB on augmenting lung inflammation and AHR were markedly diminished. These findings suggest that chronic heavy colonization of enterotoxin producing S. aureus in the skin of patients with atopic dermatitis may have an important role in the development of atopic march via an IL-17A dependent mechanism.
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Atopic dermatitis (AD) has long been associated with Staphylococcus aureus skin colonization or infection and is typically managed with regimens that include antimicrobial therapies. However, the role of microbial communities in the pathogenesis of AD is incompletely characterized. To assess the relationship between skin microbiota and disease progression, 16S ribosomal RNA bacterial gene sequencing was performed on DNA obtained directly from serial skin sampling of children with AD. The composition of bacterial communities was analyzed during AD disease states to identify characteristics associated with AD flares and improvement post-treatment. We found that microbial community structures at sites of disease predilection were dramatically different in AD patients compared with controls. Microbial diversity during AD flares was dependent on the presence or absence of recent AD treatments, with even intermittent treatment linked to greater bacterial diversity than no recent treatment. Treatment-associated changes in skin bacterial diversity suggest that AD treatments diversify skin bacteria preceding improvements in disease activity. In AD, the proportion of Staphylococcus sequences, particularly S. aureus, was greater during disease flares than at baseline or post-treatment, and correlated with worsened disease severity. Representation of the skin commensal S. epidermidis also significantly increased during flares. Increases in Streptococcus, Propionibacterium, and Corynebacterium species were observed following therapy. These findings reveal linkages between microbial communities and inflammatory diseases such as AD, and demonstrate that as compared with culture-based studies, higher resolution examination of microbiota associated with human disease provides novel insights into global shifts of bacteria relevant to disease progression and treatment.
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Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Genetic predisposition, epidermal barrier disruption, and dysregulation of the immune system are some of the critical components of AD. An impaired skin barrier may be the initial step in the development of the atopic march as well as AD, which leads to further skin inflammation and allergic sensitization. Type 2 cytokines as well as interleukin 17 and interleukin 22 contribute to skin barrier dysfunction and the development of AD. New insights into the pathophysiology of AD have focused on epidermal lipid profiles, neuroimmune interactions, and microbial dysbiosis. Newer therapeutic strategies focus on improving skin barrier function and targeting polarized immune pathways found in AD. Further understanding of AD pathophysiology will allow us to achieve a more precision medicine approach to the prevention and the treatment of AD.
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Allergic diseases have in common a dysfunctional epithelial barrier, which allows the penetration of allergens and microbes, leading to the release of type 2 cytokines that drive allergic inflammation. The accessibility of skin, compared with lung or gastrointestinal tissue, has facilitated detailed investigations into mechanisms underlying epithelial barrier dysfunction in atopic dermatitis (AD). This Review describes the formation of the skin barrier and analyzes the link between altered skin barrier formation and the pathogenesis of AD. The keratinocyte differentiation process is under tight regulation. During epidermal differentiation, keratinocytes sequentially switch gene expression programs, resulting in terminal differentiation and the formation of a mature stratum corneum, which is essential for the skin to prevent allergen or microbial invasion. Abnormalities in keratinocyte differentiation in AD skin result in hyperproliferation of the basal layer of epidermis, inhibition of markers of terminal differentiation, and barrier lipid abnormalities, compromising skin barrier and antimicrobial function. There is also compelling evidence for epithelial dysregulation in asthma, food allergy, eosinophilic esophagitis, and allergic rhinosinusitis. This Review examines current epithelial barrier repair strategies as an approach for allergy prevention or intervention.
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Staphylococcus aureus (S. aureus) is a notorious pathogen and one of the most frequent causes of biofilm-related infections. The treatment of S. aureus biofilms is hampered by the ability of the biofilm structure to shield bacteria from antibiotics as well as the host’s immune system. Therefore, new preventive and/or therapeutic interventions, including the use of antibody-based approaches, are urgently required. In this review, we describe the mechanisms by which anti-S. aureus antibodies can help in combatting biofilms, including an up-to-date overview of monoclonal antibodies currently in clinical trials. Moreover, we highlight ongoing efforts in passive vaccination against S. aureus biofilm infections, with special emphasis on promising targets, and finally indicate the direction into which future research could be heading.
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The primary care provider will commonly see skin and soft tissue infections in the outpatient setting. Skin and soft tissue infections range from the uncomplicated impetigo to the potentially lethal necrotizing fasciitis. This article reviews these infections based on their underlying etiology: bacterial, fungal, and viral causes. This article discusses the etiology, presentation, evaluation, and management of impetigo, bullous impetigo, erysipelas, cellulitis, periorbital cellulitis, orbital cellulitis, folliculitis, furuncles, carbuncles, abscess, necrotizing fasciitis, sporotrichosis, tinea corporis, tinea pedis, tinea capitis, Herpes Simplex Virus, zoster, molluscum contagiosum, and warts.
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Individuals with atopic dermatitis (AD) have used bleach baths to treat superinfections, although their mechanism of action is not well understood. The ClinicalTrials.gov, National Eczema Association, and PubMed databases were searched for studies that investigate the role bleach plays in modulating AD. Fifteen studies were included in this review. Bleach bath improves clinical symptoms of AD and restores surface microbiome by eradicating bacteria, most notably Staphylococcus aureus. Many studies have noted that this antimicrobial effect has reduced the need for topical corticosteroids or topical antibiotics. In addition, bleach seems to have strong anti-inflammatory and antipruritogenic effects. Lastly, bleach baths seem to be safe on human skin, without disrupting epidermal barrier function. Although the effects of bleach are promising, studies that investigate the long-term use of bleach alone, without concomitant AD treatment modalities, are needed. The emergence of new bleach-containing products warrants future investigations to examine their effects on cutaneous microbiome, epidermal barrier function, and immunity.