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Pleurotus citrinopileatus polysaccharide stimulates anti-inflammatory properties during monocyte-to-macrophage differentiation
Abstract
Polysaccharides from edible mushrooms possess important immunomodulating effects on immune cells including monocytes and macrophages. Macrophages activated by LPS/IFNγ are polarized toward inflammatory macrophages, whereas the anti-inflammatory properties of alternative activated macrophages play an important regulatory role in the innate immune system. We here show that the Pleurotus citrinopileatus mushroom polysaccharide (PCPS) can modulate the monocyte-to-macrophage differentiation early at the monocyte stage. Using both human THP-1 monocytic cells as well as human peripheral monocytes, we showed that PCPS inhibits the secreted levels of the pro-inflammatory cytokines TNF and IL-6, after stimulation of macrophages derived from PCPS-treated monocytes, with IFNγ + LPS. In addition, the glucan induced a tendency to increase the secreted levels of the anti-inflammatory cytokine IL-10, enhanced the expression levels of CCL2 and CCL8 mRNAs, and inhibited expression of CCR2 mRNA in the IFNγ/LPS activated macrophages. Interestingly, these data suggest that PCPS can induce a long-lasting anti-inflammatory effect in monocytes. Treatment of monocytes with laminarin and antibodies against Dectin-1 and TLR2 during PCPS treatment affected the glucan-modulated macrophage differentiation. In summary, the results of this study indicate that the glucan directs the differentiation of monocytes toward a macrophage cell population with reduced pro-inflammatory capacity via Dectin-1 and TLR2.
... In other studies involving liver diseases, carcinoma, diabetes, hypercholesterolemia and hyperlipidemia, mushroom extracts from the genus Pleurotus also showed antioxidant effects, restoring MDA levels, and increasing antioxidant defenses such as GSH, SOD, CAT, GPx, vitamin C and vitamin E. Thus, they protect the tissues against oxidative damage [34,42,[88][89][90][91][92][93][94]. ...
... Research has shown that extracts from different species of the genus Pleurotus can modulate the synthesis and release of proinflammatory mediators and reduce in the migration of total leukocytes. Therefore, it has been suggested that these extracts have anti-inflammatory properties, reducing nociception and oedema [78,[83][84][85][86][87][88][89]. ...
... Other studies have shown that b-glycan extracted from mushrooms of the genus Pleurotus exerts an immunostimulatory effect by modulating the activity of neutrophils, macrophages, monocytes, and natural killer cells [80,88]. This compound also stimulates cytokines such as interleukin-1 and tumor necrosis factor-a, resulting in an increased immune response. ...
Mushrooms are a group of fungi with great diversity and ultra-accelerated metabolism. As a consequence, mushrooms have developed a protective mechanism consisting of high concentrations of antioxidants such as selenium, polyphenols, β-glucans, ergothioneine, various vitamins and other bioactive metabolites. The mushrooms of the Pleurotus genus have generated scientific interest due to their therapeutic properties, especially related to risk factors connected to the severity of coronavirus disease 2019 (COVID-19). In this report, we highlight the therapeutic properties of Pleurotus mushrooms that may be associated with a reduction in the severity of COVID-19: antihypertensive, antihyperlipidemic, antiatherogenic, anticholesterolemic, antioxidant, anti-inflammatory and antihyperglycemic properties. These properties may interact significantly with risk factors for COVID-19 severity, and the therapeutic potential of these mushrooms for the treatment or prevention of this disease is evident. Besides this, studies show that regular consumption of Pleurotus species mushrooms or components isolated from their tissues is beneficial for immune health. Pleurotus species mushrooms may have a role in the prevention or treatment of infectious diseases either as food supplements or as sources for pharmacological agents.
Please cite this article as: dos Reis EE, Schenkel PC, Camassola M. Effects of bioactive compounds from Pleurotus mushrooms on COVID-19 risk factors associated with the cardiovascular system. J Integr Med. 2022; Epub ahead of print.
... For example, Smilax glabra Roxb. polysaccharides could effectively promote the phagocytic capacities of macrophages [10], and polysaccharides from Pleurotus citrinopileatus significantly increased the secretion of TNF, IL-6 and IL-10 by macrophages [11]. Generally, macrophages are divided into M1-type and M2type macrophages. ...
... M1-type macrophages are activated by Th1 cytokines (IFN-γ), microbial products (LPS), and endogenous stress signals (heat shock proteins). This kind of macrophage produces a large number of proinflammatory cytokines (IL-6 and TNF-α) and induces iNOS to produce NO [11,23,27]. The inflammatory response promoted by M1-type macrophages has a strong ability to kill pathogenic microorganisms and germs. ...
... It is well known that many polysaccharides have regulatory effects on macrophage activation, and some studies have also shown that polysaccharides have effects on macrophage polarization. Minato et al. [11] reported that Pleurotus citrinopileatus polysaccharides reduced the secretion of TNF and IL-6 by macrophages and increased the secretion of the anti-inflammatory cytokine IL-10, indicating that polysaccharides lead to polarization of monocytes toward the M2 macrophage subtype. In contrast, another study [23] showed that polysaccharides from Platycladus orientalis (L.) Franco leaves increased TNF-α and IL-6 levels in macrophages and decreased TGF-β levels in macrophages. ...
Polysaccharides are important components of Alpiniae oxyphyllae fructus that have been shown to exhibit significant immunomodulatory activity in our previous study. However, whether and how A. oxyphyllae fructus polysaccharides (AOFP) affect macrophages has not been determined. To further study the immunomodulatory activity of AOFP, the effect of AOFP on RAW264.7 cell activation was investigated in the present work. The results showed that AOFP2 significantly increased the phagocytic activity of RAW264.7 macrophages. AOFP2 promoted the secretion of TNF-α, IL-6, IL-10, TGF-β, NO and iNOS and enhanced the Th2-type immune response via its activation effect on macrophages. Additionally, the structure of AOFP2 was characterized in the present study, as the structural features of polysaccharides determine their biological activities. AOFP2 was only composed of glucose, exhibiting an average molecular weight of 44.3 kDa. Furthermore, the infrared spectroscopy, methylation and nuclear magnetic resonance results indicated that AOFP2 consisted of → 4)-α-D-Glcp-(1→, →4,6)-α-D-Glcp-(1 → and T-α-Glcp.
... Ken-ichiro et al. reported that Pleurotus citrinopileatus polysaccharide (PCPS) was able to regulate the monocyte-to-macrophage differentiation early at the monocyte stage [84]. PCPS could inhibit the levels of secreted pro-inflammatory cytokines (TNF and IL-6), increase the secreted levels of the anti-inflammatory cytokine IL-10, and the expression levels of CCL2 and CCL8 mRNAs, similarly constrained mRNA expression of CCR2 in the IFNγ/LPS activated macrophages [84]. ...
... Ken-ichiro et al. reported that Pleurotus citrinopileatus polysaccharide (PCPS) was able to regulate the monocyte-to-macrophage differentiation early at the monocyte stage [84]. PCPS could inhibit the levels of secreted pro-inflammatory cytokines (TNF and IL-6), increase the secreted levels of the anti-inflammatory cytokine IL-10, and the expression levels of CCL2 and CCL8 mRNAs, similarly constrained mRNA expression of CCR2 in the IFNγ/LPS activated macrophages [84]. In previous study, Ken-ichiro et al. [85] found that PCPS improved the surface maturation markers (CD80, CD86, and HLA-DR) on DCs, which suggested its potential to induce DC maturation. ...
The deficiency of chemical-synthesized antiviral drugs when applied in clinical therapy, such as drug resistance, and the lack of effective antiviral drugs to treat some newly emerging virus infections, such as COVID-19, promote the demand of novelty and safety anti-virus drug candidate from natural functional ingredient. Numerous studies have shown that some polysaccharides sourcing from edible and medicinal fungus (EMFs) exert direct or indirect anti-viral capacities. However, the internal connection of fungus type, polysaccharides structural characteristics, action mechanism was still unclear. Herein, our review focus on the two aspects, on the one hand, we discussed the type of anti-viral EMFs and the structural characteristics of polysaccharides to clarify the structure-activity relationship, on the other hand, the directly or indirectly antiviral mechanism of EMFs polysaccharides, including virus function suppression, immune-modulatory activity, anti-inflammatory activity, regulation of population balance of gut microbiota have been concluded to provide a comprehensive theory basis for better clinical utilization of EMFs polysaccharides as anti-viral agents.
... This implies that 2% crude extract of P. sajor-caju can improve some of innate immune response in carp fish, and this finding was similar with the previous studies; for instance, Safari and Sarkheil [29] found that 1.5-2% dietary administration of Pleurotus eryngii induced higher number of white blood cells, particularly, monocyte, and activities of immunoglobulin, lysozyme, and complement at 63 days of the experiment. In addition, Minato et al. [30] demonstrated that polysaccharide of eatable mushroom, Pleurotus citrinopileatus, can modulate the differentiation of monocyte to macrophage. Interestingly, Minato et al. [30] proved that the competitive inhibition of dectin-1 and toll-like receptor-2 (TLR-2) receptors for β-glucan and polysaccharide on monocyte can affect the differentiation from monocyte to macrophage. ...
... In addition, Minato et al. [30] demonstrated that polysaccharide of eatable mushroom, Pleurotus citrinopileatus, can modulate the differentiation of monocyte to macrophage. Interestingly, Minato et al. [30] proved that the competitive inhibition of dectin-1 and toll-like receptor-2 (TLR-2) receptors for β-glucan and polysaccharide on monocyte can affect the differentiation from monocyte to macrophage. In addition, Garcia-Valtanen et al. [31] showed that the supplementation of β-glucan during in vitro culture of monocytes from murine and human correlated to the increased viability and lifespan of these cells and influenced the differentiation from monocytes to macrophages at day 5 of the experiment compared to monocytes without β-glucan. ...
Aim: The present study aimed at highlighting the effects of oyster mushroom (Pleurotus sajor-caju), as a dietary supplement on growth performance, differential leukocytes population, and histological changes of melanomacrophage centers (MMCs) in spleen and kidney of fancy carp on bacterial infection.
Materials and Methods: A total of 60 fancy carp were allocated into four groups according to feed formulations including; (1) basal diet with 2% crude extract of P. sajor-caju, (2) basal diet with 2% β-glucan, whereas Group 3, and Group 4 were positive and negative control, which were fed only basal diet. Diets were provided for 30 days, thereafter, fish of Group 1 to Group 3 were intraperitoneally injected with Aeromonas veronii (1.8×109 CFU), whereas Group 4 was injected with normal saline. At day 7 post-bacterial inoculation, all fish were weighed, whole blood was collected for differential white blood cell count, and two visceral organs, posterior kidney and spleen, were collected from euthanized fish to observe histological changes, particularly MMCs.
Results: No significant differences in body weight were found (p>0.05) at 1st week of the experiment; however, fish body weight was significantly increased from week 2 to week 4 of the experiment. Increased monocyte number was found in carp fish fed with the P. sajor-caju or β-glucan supplemented diets compared to the control groups (p
... In a study by Jedinak et al. [14], Oyster Mushroom Concentrate (OMC) inhibited the release of TNF-α and IL-6, as well as modulated the NFκ B pathway. Additionally, a glucan extract from Pleurotus citrinopileatus suppressed the production of proinflammatory cytokines in human IFNγ/LPS-activated macrophages [15]. ...
Mushrooms and their bioactive compounds have demonstrated significant anti-inflammatory potential, yet their role in mitigating osteoarthritis (OA) remains underexplored. OA is a degenerative joint disease commonly affecting diarthrodial joints, leading to disability, particularly among the elderly. It is characterized by the excessive production of proinflammatory cytokines and oxidized low-density lipoproteins (oxLDLs) in chon- drocytes. This review examines existing literature on the immunomodulatory effects of edible and medicinal mushrooms, proposing their potential in reducing OA risk. Findings indicate that mushrooms can suppress inflammation by inhibiting nuclear factor kappa-B (NF-κB) and proinflammatory mediators such as cyclooxygenase-2 (COX-2), nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukins (IL-1β, IL-b), and tumor necrosis factor-alpha (TNF-α). Given that these mediators are elevated in OA, mushroom-derived compounds may alleviate OA severity by modulating their expression. However, there remains a gap in research regarding the role of microRNA and nanotechnology in OA treatment, highlighting the need for further studies. This review provides comprehensive evidence supporting the anti-inflammatory properties of mush- rooms, emphasizing their potential as an alternative therapeutic strategy for OA management. Future research should focus on the integration of microRNA and nanotechnology to enhance OA treatment efficacy.
... Additionally, accumulating evidence has shown that water extracts from P. citrinopileatus have many beneficial functions, including antitumor activity [12], immune-enhancing ability [13] and antihyperglycemic properties [14]. The polysaccharides from P. citrinopileatus fruiting bodies are important active ingredients with various activities, such as antioxidant, hepatoprotective, anti-inflammatory, immunomodulating and anti-obesity properties [15][16][17][18]. Furthermore, Musieba et al. [19] stated that P. citrinopileatus mushrooms can be an excellent source of micronutrients and antioxidant components, while Rushita et al. [14] reported that P. citrinopileatus had excellent antidiabetic activity, highlighting its great potential as an ingredient in natural health products. ...
Agricultural activities produce large quantities of organic byproducts and waste rich in lignocellulosic materials, which are not sufficiently utilized. In this study, alternative agricultural waste products, namely, spent mushroom substrate (SMS) from the cultivation of edible Pleurotus ostreatus mushrooms and the roots of leafy vegetables from hydroponic cultivation (HRL), were evaluated for their potential to be used as substrates for the cultivation of Pleurotus citrinopileatus and their effects on the quality, the nutritional value, the chemical properties (lipid, protein, carbohydrate, ash, fatty acid and carbohydrate composition) and the bioactive content (total phenolic compounds and antioxidant activity) of produced mushrooms. SMS and HRL (in different ratios with and without additives) and wheat straw with additives (WS—control) were used. During incubation, the linear growth rate of the mycelium (Kr, mm/day) was measured and used for screening. Mushroom cultivation took place in bags, where several characteristics were examined: earliness (duration between the day of substrate inoculation and the day of first harvest) and biological efficiency (B.E. %, the ratio of the weight of fresh mushrooms produced per dry weight of the substrate × 100). Furthermore, this study aimed to investigate the effect of the protein extract (PE) and carbohydrate extract (CE) of P. citrinopileatus after in vitro digestion (fraction less than 3kDa: PE-DP-3; digestate fraction: CE-D, respectively) on the expression of antioxidant-related genes in the THP-1 cell line. The results showed that mushrooms grown on SMS 50%-HRL 40% had the fastest growth (6.1 mm/d) and the highest protein and lipid contents (34.7% d.w.; 5.1% d.w.). The highest B.E. (73.5%), total carbohydrate (65.7%) and total phenolic compound (60.2 mg GAE/g d.w.) values were recorded on the control substrate. Antioxidant activity was observed in all extracts; the total flavonoid content was low in the samples, and the maximum total triterpene value was detected in SMS 80%-HRL 20% (9.8 mg UA/g d.w.). In all mushrooms, linoleic acid (C18:2) was the main fatty acid (above 60%), and fructose was the dominant individual saccharide. In the investigation of the regulation pathway, NFE2L2 gene expression was upregulated only in the SMS 60%-HRL 40% intervention during incubation with CE-D samples. Additionally, the transcription levels of antioxidant-related genes, SOD1, CAT, HMOX1 and GSR, were increased in the SMS 60–30% intervention. Compared to WS, the alternative substrates are observed to trigger a pathway concerning CE that may resist oxidative stress. This study supports the utilization of agricultural byproducts through sustainable and environmentally friendly practices while simultaneously producing high-value-added products such as mushrooms. Therefore, alternative substrates, particularly those containing HRL, could serve as natural sources of antioxidant potential.
... The anti-inflammatory effect of glucan isolated from P. pulmonaris was examined by acetic acidinduced writhing reaction in mice, which is a typical model to measure inflammatory pain, and it was observed that the glucan inhibits leukocyte migration to damaged tissues (Smiderle et al., 2008). Minato, Laan, van Die & Mizuno (2019) reported that the P. citrinopileatus polysaccharide can inhibit the secretion of pro-inflammatory cytokines and chemokines in LPS/IFN activated macrophages and promote the expression of the antiinflammatory cytokine interleukin-10. Some immunomodulator compounds have been isolated from P. eryngii. ...
... Polysaccharide from P. citrinopileatus (PCPS) inhibited the secretion of pro-inflammatory cytokines and chemokines by macrophages activated by LPS/INF-γ, and promoted the expression of anti-inflammatory cytokine IL-10. The antiinflammatory effect was related to Dectin-1 and TLR2 receptors (Minato et al., 2019). There is growing evidence that certain miRNAs play key regulatory roles in macrophage activation and inflammation. ...
Edible fungus polysaccharides have garnered significant attention from scholars due to their safety and potential anti-inflammatory activity. However, comprehensive summaries of their anti-inflammatory properties are still rare. This paper provides a detailed overview of the anti-inflammatory effects and mechanisms of these polysaccharides, as well as their impact on inflammation-related diseases. Additionally, the relationship between their structure and anti-inflammatory activity is discussed. It is believed that this review will greatly enhance the understanding of the application of edible fungus polysaccharides in anti-inflammatory treatments, thereby significantly promoting the development and utilization of edible fungi.
... Dietary fiber (DF), which consists mainly of pectin, lignin, resins, pentaglycine, cellulose and hemicellulose, is defined as a multiple-unit carbohydrate polymer, a polysaccharide that is not digested by human intestinal enzymes (Minato, Laan, Die, & Mizuno, 2019;Sheng et al., 2019;Wang et al., 2021). DFs are naturally found in cereals, vegetables, fruits and nuts. ...
Dietary fiber (DF) is an important active polysaccharide in Hericium erinaceus. Obesity can lead to a wide range of diseases. In this work, we investigated the in vitro lipid-lowering effect of soluble dietary fiber (SDF) from H. erinaceus, aiming to provide a basis for the subsequent development of lipid-lowering products. Ultrasound-assisted enzymatic extraction (UAEE) of SDF from H. erinaceus was performed. The optimal extraction parameters determined via single-factor experiments and response surface methodology (RSM) were as follows: Lywallzyme concentration, 1.0%; complex protease concentration, 1.2%; ultrasonication time, 35 min; and ultrasonication power, 150 W. In vitro lipid-lowering experiments revealed that the adsorption amount of cholesterol micelles by H. erinaceus SDF was 11.91 mg/g. The binding amount and binding rate of sodium taurocholate were 3.73 mg/g and 42.47%, respectively, and those of sodium glycocholate were 3.43 mg/g and 39.12%, respectively. The pancreatic lipase inhibition rate reached 52.11%, and the type of inhibition was competitive. Therefore, H. erinaceus SDF has good in vitro lipid-lowering ability.
... Fungal metabolites have historically been categorized into primary, that is, metabolites essential for growth and reproduction, and secondary, which are considered to be rich sources of potential drug candidates and other useful substances [3,4]. According to the literature, the fruit body of PCS is rich in metabolites such as polysaccharides, phenols, flavonoids, terpenoids and alkaloids [5,6], with potential pharmacological activity against neoplastic [3], displays antioxidant activities [3], immune regulatory effects [7], and it has a key role in regulating blood sugar [8] and lowering blood pressure and cholesterol [9]. Meanwhile, the lectin extract from the PCS fruit body exhibits potent anti-inflammatory effects [10]. ...
Pleurotus citrinopileatus Singer (PCS) has attracted increasing attention as a raw material for medicine and food. Its quality is greatly affected by the accumulation of metabolites, which varies with the applied drying methods. In this study, we utilize an approach based on ultra-high-performance liquid chromatography/Q Exactive mass spectrometry (UHPLC-QE-MS) to reveal the metabolic profiles of PCS from three different drying methods (natural air-drying, NAD; hot-air-drying, HAD; vacuum freeze-drying, VFD). The results showed that lipids, amino acids and their derivatives were all important secondary metabolites produced during NAD, HAD and VFD treatments, with the key differential metabolites of PCS during drying including fifteen lipids and seven amino acids. Meanwhile, VFD was the best way for long-term preservation of dried PCS. Hot-drying methods, especially HAD, can improve the medicinal component of PCS. Furthermore, KEGG enrichment analysis highlighted 16 pathways and indicated that amino acid metabolism might be the key metabolite pathway for the PCS drying process. Our study elucidates the relationship between drying methods and metabolites or metabolic pathways of PCS to determine the mechanisms affecting the quality of PCS, and finally provides reference values for further development and application in functional food and medications.
... Additionally, colonic, and ileal tissues underwent the same assessment for senescence markers. The details of primers' sequence were retrieved from previous studies (25)(26)(27); primer details are presented in Supplementary Table S1. ...
Introduction
Cognitive decline is a common consequence of aging. Dietary patterns that lack fibers and are high in saturated fats worsen cognitive impairment by triggering pro-inflammatory pathways and metabolic dysfunctions. Emerging evidence highlights the neurocognitive benefits of fiber-rich diets and the crucial role of gut-microbiome-brain signaling. However, the mechanisms of this diet-microbiome-brain regulation remain largely unclear.
Methods
Accordingly, we herein investigated the unexplored neuroprotective mechanisms of dietary pulses-derived resistant starch (RS) in improving aging-associated neurocognitive function in an aged (60-weeks old) murine model carrying a human microbiome.
Results and discussion
Following 20-weeks dietary regimen which included a western-style diet without (control; CTL) or with 5% w/w fortification with RS from pinto beans (PTB), black-eyed-peas (BEP), lentils (LEN), chickpeas (CKP), or inulin fiber (INU), we find that RS, particularly from LEN, ameliorate the cognitive impairments induced by western diet. Mechanistically, RS-mediated improvements in neurocognitive assessments are attributed to positive remodeling of the gut microbiome-metabolome arrays, which include increased short-chain fatty acids and reduced branched-chain amino acids levels. This microbiome-metabolite-brain signaling cascade represses neuroinflammation, cellular senescence, and serum leptin/insulin levels, while enhancing lipid metabolism through improved hepatic function. Altogether, the data demonstrate the prebiotic effects of RS in improving neurocognitive function via modulating the gut-brain axis.
... DF, which mostly consists of pectin, lignin, resin, pentaglycine, cellulose, and hemicellulose, is defined as multiple units of carbohydrate polymers, a type of polysaccharide that is not digested by human intestinal enzymes [13][14][15]. DFs are found naturally in grains, vegetables, fruits, and nuts. DF is the seventh most abundant nutrient investigated by the scientific community, and its significance for our bodies is clear. ...
Pleurotus citrinopilestus contains a variety of physiologically and pharmacologically active compounds. A key active component among these compounds is dietary fiber, a polysaccharide that exhibits several biological properties. The objective of this study was to assess how soluble dietary fiber (SDF) from Pleurotus citrinopilestus responded to ultrasonic-assisted enzymatic (UAE) extraction. The response surface method (RSM) combined with the Box-Behnken design method (BBD) was used to optimize the yield of SDF. The effects of the liquid-solid ratio (35–55 mL/g), α-amylase concentration (0.5–2.5%), complex protease concentration (0.4–2.0%), and ultrasonication time (15–55 min) on the yield of SDF were examined. The RSM results revealed the optimal liquid-solid ratio (45 mL/g), α-amylase concentration (1.5%), complex protease concentration (1.2%), and ultrasonic time (35 min). The SDF yield was 10.25%, which is close to the predicted value (10.08%).
... It is also used as a component in other medicinal preparations (Oyetayo, 2011;Soro et al., 2019;Yongabi et al., 2004) Lentinus Fat removal, antibiotic and antineoplastic (Oyetayo, 2011;Soro et al., 2019) medicinal mushrooms, exhibiting different spectrum of bioactivities, such as antitumor, anti-proliferative, antidiabetic, anti-inflammatory, and antimicrobial assets. In this class of compounds, special emphasis must be given to glucans, mainly β-glucans, which perform different bioactivities, such as antimicrobial and hypoglycemic, also promoting the boost of immunity through the production of activating macrophages (Disler et al., 2019;Minato et al., 2019;Yang et al., 2018). The presence of glucans has been reported in different species of wild mushrooms, such as Pleurotus pulmonarius and P. tuber-regium, namely mannogalactoglucan, xyloglucan (Reis et al., 2012), while other polysaccharides such as tremellastin and tchizophyllan were identified in Tremella fuciformis and Schizophyllum commune, respectively (Reis et al., 2012). ...
The Himalayan region of Jammu and Kashmir constitutes a natural depository of the rich biodiversity of India. Mushrooms are non-timber forest resources that have been utilized as a source of food since time immemorial, but only a few species are used for pharmaceutical purposes due to the absence of scientific information and indigenous knowledge. If identified properly, these mysterious specimens could be used for numerous ailment prevention and treatment methods. In this chapter, 20 mushroom species found to have a wide range of bioactive chemicals and great medicinal potential are identified. All these species are described based on their morphological details, along with habit, habitat, traditional names, medicinal properties, and ethnomycological uses.
... The modulatory effect of mushroom polysaccharides in human dendritic cells was found to be significantly augmented through the activation of TLR4 and further enhanced synergistically upon stimulation of TLR2. These findings indicate that the interaction between PCPS and these TLRs plays a crucial role in the observed modulation of dendritic cells [51]. ...
Since ancient times, mushrooms have been considered valuable allies of human well-being both from a dietary and medicinal point of view. Their essential role in several traditional medicines is explained today by the discovery of the plethora of biomolecules that have shown proven efficacy for treating various diseases, including cancer. Numerous studies have already been conducted to explore the antitumoural properties of mushroom extracts against cancer. Still, very few have reported the anticancer properties of mushroom polysaccharides and mycochemicals against the specific population of cancer stem cells (CSCs). In this context, β-glucans are relevant in modulating immunological surveillance against this subpopulation of cancer cells within tumours. Small molecules, less studied despite their spread and assortment, could exhibit the same importance. In this review, we discuss several pieces of evidence of the association between β-glucans and small mycochemicals in modulating biological mechanisms which are proven to be involved with CSCs development. Experimental evidence and an in silico approach are evaluated with the hope of contributing to future strategies aimed at the direct study of the action of these mycochemicals on this subpopulation of cancer cells.
... It is also used as a component in other medicinal preparations (Oyetayo, 2011;Soro et al., 2019;Yongabi et al., 2004) Lentinus Fat removal, antibiotic and antineoplastic (Oyetayo, 2011;Soro et al., 2019) medicinal mushrooms, exhibiting different spectrum of bioactivities, such as antitumor, anti-proliferative, antidiabetic, anti-inflammatory, and antimicrobial assets. In this class of compounds, special emphasis must be given to glucans, mainly β-glucans, which perform different bioactivities, such as antimicrobial and hypoglycemic, also promoting the boost of immunity through the production of activating macrophages (Disler et al., 2019;Minato et al., 2019;Yang et al., 2018). The presence of glucans has been reported in different species of wild mushrooms, such as Pleurotus pulmonarius and P. tuber-regium, namely mannogalactoglucan, xyloglucan (Reis et al., 2012), while other polysaccharides such as tremellastin and tchizophyllan were identified in Tremella fuciformis and Schizophyllum commune, respectively (Reis et al., 2012). ...
In several regions of Africa, the daily diet is partly dependent on the edible products from wild animals, plants, and mushrooms, driven by their availability, wide distribution in the local environment, and the low incomes of the general population. The documentation of ethnomycological information is particularly important to validate or correct the identification of specimens and the preservation of these natural resources with cultivation potential, thus improving their consumption and utilization for medicinal purposes. The number of wild edible mushroom species consumed varies between different regions of Africa, with around 300 species being documented in the literature. However, despite its rich biodiversity, the African continent is still underexploited, which is reflected in poor food contribution to populations that are often in need. Here, the safe use of mushrooms is guided by the insufficiency of studies that validate their nutritional and medicinal properties, since they are key factors in the suppression of protein deficiency in the everyday diet of the populations and a source of bioactive compounds useful for the formulation of added‐value functional products. Thus, it becomes essential to investigate African mushrooms, not only from the identification point of view, but also in terms of nutritional, chemical, and bioactive characterization, hence deepen the knowledge about this valuable natural resource. Bearing these in mind, the main objective of this study is to systematize the knowledge available in scientific publications and specialized websites, thus gathering information about the valuable profits that come from using these widely appreciated natural products.
... Основну групу сполук у фунгітерапії, що володіють антиоксидантними, протипухлинними, протидіабетичнми, протизапальними, антимікробними, противірусними та імуномодулюючими активностями представляють полісахариди [8,9]. Полісахариди глюкану, особливо β-глюкану, виявляють бактерицидну, гіпоглікемічну активності, здатні покращувати імунну реакцію організму завдяки активації макрофагів [11]. Терпени є компонентами, що серед інших біологічно активних речовин грибів, здатні проявляти антиоксидантні, протипухлинні та протизапальні активності [12]. ...
Вагомим критерієм при виборі певних штамів грибів для їх промислового культивування є їх бактерицидні та фунгіцидні властивості. Метою роботи було проаналізувати деякі штами грибів на предмет їх здатності протидіяти Penicillium sp. в умовах конфронтації. В результаті проведених досліджень рівнозначні антагоністичні властивості встановлені між мікроміцетом та Polyporus umbellatus 2511, 2510, Sparassis nemecii 2327. Антагоністичні властивості мікроміцета переважають у бінарних композиціях Penicillium sp.− Hericium coralloides 2332, 2333, Penicillium sp. – Flammulina velutipes CU. Видами, які видаються перспективними у плані подальшого їх використання для культивування та/чи дослідження їх фунгіцидних властивостей є Sparassis laminоsa 2211 та Fomitopsis оfficinalis 5004, 2498, 2497, антагоністичні властивості яких переважають при спільному культивуванні із мікроміцетом.
... Yin et al., 2019), making it a suitable material to prepare highquality flavor condiments. However, in recent years, most studies of P. citrinopileatus have concentrated on its biological activity evaluation and genetic diversity, whereas few reports focusing on the utilization of flavor compounds in P. citrinopileatus have been conducted (Minato et al., 2019;Rosnina et al., 2016;Sheng et al., 2019). ...
Pleurotus citrinopileatus, a nutritious and palatable edible mushroom, can be used as an appropriate material to prepare high‐grade flavoring agents. Based on this, the current study aimed to investigate the feasibility of a productive protease system from Actinomucor elegans to prepare P. citrinopileatus hydrolysate (PCH). The Actinomucor elegans crude protease (AECP) was prepared from the solid‐state fermentation product of P. citrinopileatus by A. elegans. AECP and four commercial proteases (alcalase, neutrase, papain, and protamex) were applied to acquire five kinds of PCHs. The physical‐chemical properties of PCHs as well as its concentration and composition of nonvolatile compounds were comparatively analyzed. Sensory evaluation and electronic tongue analysis were utilized to evaluate sensory characteristics. AECP was found to be the most effective protease, with the highest hydrolysis degree (35.91%) and protein recovery (81.46%). The result of molecular weight distribution indicated that peptides below 500 Da were the main fraction of AECP hydrolysates, while AECP hydrolysates showed the highest content of monosodium glutamate‐like (20.23 ± 0.16 mg/g) and flavor 5′‐nucleotide (4.30 ± 0.07 mg/g) peptides. In summary, the AECP hydrolysate had superior sensory profiles compared with other hydrolysates. In addition, AECP hydrolysates exhibited favorable kokumi taste in which peptides below 500 Da showed the highest correlation with kokumi by the results of partial least‐squares regression. These results indicated the feasibility of applying PCHs as flavor additives or seasoning in the food industry. AECP might be used as an alternative enzyme choice because of its low cost and high hydrolysis efficiency.
Practical Application
Pleurotus citrinopileatus served as a potential raw material for natural seasonings because of its high protein content and appropriate ratio of umami amino acids to total amino acids. Enzymatic hydrolysis was an efficient approach to improve the flavor of P. citrinopileatus, where the choice of enzyme was one of the most critical factors. The research indicated that P. citrinopileatus hydrolysate prepared by A. elegans crude protease (AECP) exhibited an acceptable flavor, which provided theoretical support for the high‐value utilization of P. citrinopileatus as food seasoning. AECP might be applied as an alternative enzyme resource because of its low cost and high hydrolysis efficiency.
... Pleurotus citrinopileatus, commonly known as golden oyster mushroom, is a basidiomycete fungus of the family Pleurotaceae and is native to Japan, northern China, and eastern Russia [1,2]. The genus Pleurotus are medicinal, ecologically, and economically critical edible fungi widely cultivated in China [2][3][4]. P. citrinopileatus is well-liked in Asian nations because of its great nutritious content, distinctive avor, bright yellow color, and anti-cholesterol and anti-diabetic properties [5]. Pleurotus species can be affected by many pathogens, including fungi, bacteria, and viruses, which can cause serious diseases [6-8]. ...
The complete genome sequence of a novel single-stranded [+ssRNA] positive-sense (+) RNA mycovirus, designated as "Pleurotus citrinopileatus ourmiavirus 1" (PcOV1), isolated from the Pleurotus citrinopileatus strain CCMJ2141, was determined. The complete genome of PcOV1 is composed of 2,535 nucleotides long. It contains a single open reading frame (ORF), which encodes a protein of 657 amino acids (aa) showing conserved domains of RNA-dependent RNA polymerase (RdRp). Phylogenetic analysis based on the RdRp revealed that PcOV1 is a new member of the genus ourmiavirus in the family Botourmiaviridae . This is the first virus characterized in P . citrinopileatus .
... In addition, the polysaccharides of P. eryngii demonstrate antioxidant, anti-tumor, antibacterial, anti-hyperlipidemic, and immunoregulatory activities [35]. The immunomodulating effects of P. eryngii polysaccharides have been investigated using different immunocompetent cells, such as monocytes and macrophages [36]. Macrophages are dynamic and heterogeneous cells. ...
Recent studies have revealed the crucial role of several edible mushrooms and fungal compounds, mainly polysaccharides, in human health and disease. The investigation of the immunomodulating effects of mushroom polysaccharides, especially β-glucans, and the link between their anticancer and immunomodulatory properties with their possible prebiotic activity on gut micro-organisms has been the subject of intense research over the last decade. We investigated the immunomodulating effects of Pleurotus eryngii mushrooms, selected due to their high β-glucan content, strong lactogenic effect, and potent geno-protective properties, following in vitro fermentation by fecal inocula from healthy elderly volunteers (>60 years old). The immunomodulating properties of the fermentation supernatants (FSs) were initially investigated in U937-derived human macrophages. Gene expression as well as pro- (TNF-α, IL-1β) and anti-inflammatory cytokines (IL-10, IL-1Rα) were assessed and correlated with the fermentation process. The presence of P. eryngii in the fermentation process led to modifications in immune response, as indicated by the altered gene expression and levels of the cytokines examined, a finding consistent for all volunteers. The FSs immunomodulating effect on the volunteers’ peripheral blood mononuclear cells (PBMCs) was verified through the use of cytometry by time of flight (CyTOF) analysis.
... From our study, we had successfully adding the value where polysaccharides extracted from mycelium and cultured broth of THR2 also demonstrated a significant antibacterial activities. Since the ENS and EPS characterized in this study were confirmed as β-glucan, thus under specific conditions, mushroom β-glucan with β-linkage has been shown to stimulate the human immune system and modulate the immunological response, making β-glucans popularly known as biological response modifiers (BRM) (Friedman et al., 2016;Minato et al., 2019). As a results of the activation of the host's immune system, the β-glucan showed significant antibacterial properties (Villares et al., 2012). ...
During the monsoon season, a wild-termite mushroom Termitomyces heimii RFES 230662 (THR2) was successfully isolated from Negeri Sembilan, Malaysia. The mushroom was morphologically labelled based on its stipe, pileus, and the budding mycelia from the termites nest. Genetic component of THR2 (300 bp) was sequenced and found to be 99% identical to Termitomyces sp. strain. The evolutionary distance (Knuc) of the isolate justified THR2 as T. heimii species. Two THR2 extracts were prepared from fruiting body (FB) and mycelial biomass (MB) for antimicrobial responses. THR2 was cultivated in a submerged-fermentation (SF) producing 8.55 g/L of MB, 0.80 g/L of endopolysaccharide (ENS) and 1.44 g/L of exopolysaccharide (EPS), respectively. For THR2-FB, two ENS extracts were obtained using hot (3.20 g/L) and cold-water (1.36 g/L) treatments. FTIR spectra analysis verified all polysaccharide as β-glucan when compared to laminarin standard. Those β-glucan possess antibacterial properties with highest response shown by ß-glucan-FB compared to ß-glucan-MB extracts. These findings serve as the blueprint for the production of β-glucan from a rare termite mushroom.
... In clinical practice, bioactive fungal polysaccharides have been a research hotspot in recent years (Giavasis, 2014). Polysaccharides from edible fungi have good effects on antioxidant , anti-cancer (Hereher, ElFallal, Toson, Abou-Dobara, & Abdelaziz, 2018), anti-inflammatory (Hua et al., 2018;Minato, Laan, Die, & Mizuno, 2018), hypoglycemic (Zhang et al., 2018), and lipidemic (Xu et al., 2017) activities. Studies have found that polysaccharides can further improve the effect of colitis by regulating gut microbiota (Ren et al., 2018;Sun et al., 2020). ...
This study aimed to evaluate whether the whole powder (SRPW) and polysaccharide (SRPS) from Sporisorium reilianum could modulate the gut microbiota in mice with dextran sulfate sodium (DSS) induced colitis. The results showed that the disease and structure of colon tissue were improved, and the balance of colonic mucosal related factors was restored. Compared to ulcerative colitis (UC) mice, the composition and diversity of gut microbiota were significantly increased. Specifically, the abundance of Bacteroidetes, TM7, and Proteobacteria at the phylum level and Bacteroides, Coprobacillus, Streptococcus, and Lactobacillus at the genus level were restored to normal levels. Furthermore, functional analysis revealed that carbohydrate, amino acid, and energy metabolism were regulated by S. reilianum, thus promoting the recovery of the intestinal mucosal structure. These findings indicated the possibility of S. reilianum as a functional food to prevent colitis through the gut microbiota.
... Bioactive molecules from mushrooms can generally be categorised into two classes; high molecular weight compounds, which include primarily polysaccharides and proteins and low molecular weight compounds, such as indoles, terpenoids and phenols. Polysaccharides represent the major group of bioactive compounds existing in mushrooms, exhibited cytotoxic, anticancer, antidiabetic, antimicrobial, and anti-inflammatory activities (Friedman, 2016;Minato et al. 2019;Wong et al. 2007). ...
Termitomyces heimii is a highly cherished wild edible mushroom in India for its pleasant delicacy, rich proximate compositions and profound ethno medicinal applications. A water soluble crude polysaccharide fraction (THP-I) was isolated from dried fruit bodies of T. heimii and purified by GPC. The ¹H- NMR spectrum of THP-I exhibited anomeric protons within chemical shifts (δH) between 3.40 to 4.0, indicating that the compound possess –CH and –CH2 functional groups, which resonate with the oxygen atoms of the –OH group, confirmed it as a polysaccharide. THP-I exhibited the MIC values of 62.5 and 125 g/ml against Staphylococcus aureus and Shigella flexneri respectively. DPPH and FRAP assays showed effective radical scavenging potential by THP-I. In vitro cytotoxicity of THP-I was evaluated by MTT assay and showed notable cellular toxicity against HCT cells at a dose concentration 200 g/ml. It is first time reported herein that, THP-I has effectively diminished hyperplasia in 1, 2-dimethylhydrazine (DMH) induced colon cancer of Swiss albino rats along with sprouting of goblet cells. Through the present study it is evident that polysaccharide from T. heimii exhibited manifold bioactivities and therefore could be exploited further for its undiscovered potential applications.
... The results showed a reduction in all measured cytokines in CMP groups compared to the DNBS group in dose dependent manner (Fig. 6), which is consistent with the results obtained in the macroscopic damage score and MPO activity. This is due to the cascade of anti-inflammatory properties of β-glucan in gut inflammation, which may correlate with the ability the β-glucan to reduce the expression of pro-inflammatory genes (Minato, Ohara, & Mizuno, 2017) the secretion of pro-inflammatory cytokines (Minato, Laan, van Die, & Mizuno, 2019) and suppression of other inflammatory related incidents (Cao et al., 2018). ...
Phallus atrovolvatus is a wild edible mushroom which is recently being cultivated in Thailand. It contains a remarkable amount of β-(1,3–1,6)-glucan, a compound known for its immune modulating properties. Crude mushroom polysaccharide (CMP) was obtained from the fruiting body of P. atrovolvatus using boiling water extraction, followed by overnight ethanol cold precipitation. CMP is composed of approximately 50% β-glucan, α-glucan, proteins, ash and other non-digestible polysaccharide. In this study, we evaluated the immune modulating activities of CMP using in vitro and in vivo models. In vitro, CMP was treated with the transfected NF-κB reporter-HEK 293 recombinant cell line, the results showed no cytotoxicity up to 500 μg/mL, and CMP treatments exhibited a higher % NF-κB luciferase expression. DiNitroBenzene Sulfonic acid (DNBS)-induced colitis mice model was used to elucidate the effects of CMP in vivo. Colitis severity was assessed using body weight trend, macroscopic scores and histological scores. Myeloperoxidase (MPO) activity and cytokine production were determined from the colon tissue and spleen, respectively. The results showed that oral consumption of 50 μg CMP/mouse/day could significantly decrease MPO activity and reduce the secretion of TNF-α, IL-6, IL-10, and IL-17A cytokines. To our knowledge, this study shows the first time the report of immune modulating activities of Phallus atrovolvatus Thai strain. The results lead to the conclusion that CMP provides two modes of actions: i) stimulating the NF-κB pathway and ii) acting as an anti-inflammatory that can protect mice against induced colitis.
In the past few years, much research has been conducted on edible mushrooms, among which Pleurotus ostreatus (PO)—also known as oyster mushrooms—has received attention due to its many health and medicinal benefits. Some research has shown that PO and its active compounds, such as lectins, polysaccharides, primarily β-glucans, phenols, polyphenols, terpenoids, ergosterols, and glycoproteins, are strong immune system modulators, have anti-inflammatory properties, and have potentially positive effects on the cardiovascular system and athletic performance. In this narrative review, an extensive search (academic databases from inception to April 25, 2024) was conducted in the scientific literature, and various aspects of PO and its effects on health and athletic performance were investigated. This narrative review article thereby demonstrates the potential benefits of PO for improving the overall baseline health and concomitant athletic sports performance, recovery, and cardiovascular system function. In addition to potential enhancements in antioxidant defense, substrate metabolism, and being a rich source of many essential nutrients, we describe a possible positive relationship between PO intake and improved athletic performance and recovery in athletes after intense exercise by reducing inflammation, modulating the microbiome, neutralizing free radicals, and strengthening the cardiovascular system. However, more research in basic studies and clinical trials is needed to investigate PO’s clinical applications, mechanisms, and effects on athletes.
A fungal strain (X21156) collected in Tibet was used as the material, identified based on its morphological characteristics and internal transcribed spacer (ITS) sequence; its optimal culture conditions were analyzed by single-factor experiments; artificial domestication and cultivation were carried out; its nutrient composition was determined; and the bioactivities of its polysaccharides were detected using chemical antioxidant assays and MTT assays. The results showed that the strain was Pleurotus citrinopileatus Sing. Its optimal culture conditions were a pH of 7, a temperature of 25 °C, glucose (20 g·L−1) as the carbon source, and yeast powder (20 g·L−1) as the nitrogen source. The fresh weight of a single domesticated fruiting body was 41.16 g. The strain had high protein (28.5%), high fiber (34%), and low fat (1.4%) contents, with high proportions of fresh and sweet amino acids. Polysaccharides had good scavenging ability on ABTS+, DPPH, and OH free radicals (EC50 0.06 mg/mL, 1.21 mg/mL, and 3.62 mg/mL, respectively), and the cytotoxicity of polysaccharides to hepatocellular carcinoma cells (HepG2) (IC50: 1.69 mg/mL) was higher than that of triple-negative breast cancer cells (MDA-MB-468) (IC50: 1.76 mg/mL). In conclusion, the study provides a reference on the optimal culture conditions, domestication and cultivation, and dietary and medicinal values of wild P. citrinopileatus Sing.
The use of fungal polysaccharides as immunomodulators has garnered significant interest. Here, the polysaccharide PCP‐1 is isolated and purified from the fruiting bodies of Pleurotus citrinopileatus . PCP‐1 is identified as a glucan with a molecular weight of 1670 kDa. Methylation analysis reveals that PCP‐1 consists of T‐Glc p , T‐Rha p , 1,3‐Glc p , 1,4‐Glc p , 1,4,6‐Glc p , and 1,3,6‐Glc p . PCP‐1 exhibits exceptional immunomodulatory effects, as it can dose‐dependently stimulate phagocytosis and promote the secretion of nitric oxide and reactive oxygen species in RAW264.7 cells. Additionally, PCP‐1 significantly enhances the secretion of cytokines such as TNF‐ α , IL‐1 β , and IL‐6 at both the protein and mRNA levels, with concentrations ranging from 2.5 to 40 µg mL ⁻¹ . At a concentration of 40 µg mL ⁻¹ , the immunomodulatory effects are comparable to those of the positive control. Furthermore, PCP‐1 promotes the nuclear translocation of the p65 protein, indicating activation of the NF‐κB signaling pathway. The results demonstrate that PCP‐1 has the potential as a natural immunomodulator, with possible applications in the food, pharmaceutical, and other industries.
Mushrooms contain many different biologically active compounds. The immunomodulatory action of mushroom β-glucans has been shown. Native liquids of mushroom cultivation can be sources of different valuable enzymes with significant potential for use in medicine and pharmacology.
As immune regulators, cytokines serve critical role as signaling molecules in response to danger, tissue damage, or injury. Importantly, due to their vital role in immunological surveillance, cytokine therapy has become a promising therapeutics for cancer therapy. Cytokines have, however, been used only in certain clinical settings. Two key characteristics of cytokines contribute to this clinical translational challenge: first, they are highly pleiotropic, and second, in healthy physiology, they are typically secreted and act very locally in tissues. Systemic administration of the cytokines can consequently result in serious side effects. Thus, scientists have sought various strategies to circumvent theses hurdles. Recent in vivo reports signify that cytokine delivery platforms can increase their safety and therapeutic efficacy in tumor xenografts. Meanwhile, cytokine delivery using multipotent stem cells, in particular mesenchymal stem/stromal cells (MSCs), and also a diversity of particles and biomaterials has demonstrated greater capability in this regards. Herein, we take a glimpse into the recent advances in cytokine sustained delivery using stem cells and also biomaterials to ease safe and effective treatments of a myriad of human tumors.
i>Pleurotus citrinopileatus , also known as golden oyster mushroom, is a newly industrialized edible mushroom mainly distributed in East Asia. It is a kind of saprophytic edible fungus with strong degradation characteristics, commonly found on fallen trees and stumps of broad-leaf tree species. So far, abundant kinds of bioactive compounds such as polysaccharides, ergothioneine, sesquiterpenes, and glycoprotein have been isolated from P. citrinopileatus and studied. Studies have confirmed that these compounds are beneficial to human health. In this paper, the recent studies on the cultivation, degradation characteristics application, and health effects of P. citrinopileatus are reviewed, and their development trends are discussed.
The complete genome sequence of a novel single-stranded [+ ssRNA] positive-sense (+) RNA mycovirus, designated as "Pleurotus citrinopileatus ourmiavirus 1" (PcOV1), isolated from Pleurotus citrinopileatus strain CCMJ2141, was determined. The complete genome of PcOV1 is composed of 2,535 nucleotides. It contains a single open reading frame (ORF), which encodes a protein of 657 amino acids (aa) containing conserved domains of an RNA-dependent RNA polymerase (RdRp). Phylogenetic analysis based on RdRp sequences revealed that PcOV1 is a new member of the genus Ourmiavirus in the family Botourmiaviridae. This is the first virus from P. citrinopileatus to be characterized.
Edible fungus are widely eaten because of their delicious taste and high nutritional value. Growing evidence indicates that edible fungus are rich in various active ingredients including polysaccharides, proteins, fats, vitamins, and other ingredients. Polysaccharide is one of the main active ingredients of edible fungi. Increasing researches have confirmed that edible fungus polysaccharides (EFPs) showed multiple biological activities such as antioxidant, anti‐inflammatory, anti‐tumor, immune regulation, anti‐virus, gut microbiota regulation, hypoglycemic, etc. Hence, EFPs related researches have received more and more attention due to their non‐toxic, high medical and nutritional values. This paper reviews the latest research progress of EFPs biological activities, and looks forward to their future development trend. This review provides a theoretical basis for studying the application of EFPs in the fields of biomedicine, cosmetics, and health food, and promotes the development and utilization of EFPs. This article is protected by copyright. All rights reserved
To convert this underutilized P. citrinopileatus which is well known for its savory taste into the high value-added food ingredients, the influence of different sulfur-containing compounds, including l-cysteine (Cys), l-methionine (Met) and thiamine (Thi) on the structure, sensory profiles and antioxidant activities of Maillard Reaction products (MRPs) obtained from P. citrinopileatus was evaluated and compared. Sulfur-containing substances significantly enhanced the Maillard reaction progress and antioxidant activities of MRPs. Cys-MRPs showed the strongest fluorescence intensity and the lowest particle size. Partial least squares regression (PLSR) analysis showed that thiols and Maillard peptides formed in Cys-MRPs exhibited meat-like aroma, kokumi and umami taste, while Met-MRPs exhibited caramel-like aroma attributed to the formation of furans. Therefore, the improvement of MRPs obtained from P. citrinopileatus with various sulfur-containing substances could increase their industrial potential as flavor enhancers with higher antioxidant activities.
Macrophages derived from human monocytic leukemia THP-1 cell line are often used as the alternative of human primary macrophage. However, the polarization method of THP-1 to macrophages varies between different laboratories, which may unknowingly affect the relevance of research output across research groups. In this regard, a systematic search was developed in Pubmed, BioOne, Scopus, and Science Direct to identify articles focusing on THP-1 polarization into M1 and M2 macrophage. All selected articles were read and discussed by two independent reviewers. The selection process was based on selected keywords on the title, abstract and full-text level. A total of 85 articles were selected and categorized based on the field of studies, method of THP-1 differentiation, and markers or genes expressed upon differentiation. THP-1 derived macrophages were mainly used together with primary monocyte-derived macrophages in cellular inflammation studies, while it was commonly employed alone in cancer research. THP-1 derived macrophages are also of paramount importance in biomaterials studies to prevent unfavorable immune responses in-vivo. We explored various methods of THP-1 differentiation and suggested several common genes encountered to characterize M1 and M2 macrophages differentiated from THP-1. The systematic review highlights the relevance of using THP-1 derived macrophage as a useful alternative to primary macrophage. Although it is not possible to derive a standard method of THP-1 polarization into M1 and M2 macrophage from this review, it may lead researchers to obtain reproducible polarization protocol based on commonly used stimulants and markers of differentiation.
Mushrooms are among the few natural products that have been relied upon for prophylactic and therapeutic applications in human diseases. They have been referred to as forest gems since they can be picked in the wild or better domesticated for appropriate use. Several scientific studies have been conducted to establish claimed potentials or further probe new areas into which mushrooms can find application. Many disciplines, including mycology, microbiology, physiology, chemistry, genetics, and medicine, among others, conduct research on mushrooms. These enable broad and in-depth studies of mushrooms, to include in vitro and in vivo demonstrations of their bioactivity, structural characterization, and isolation of bioactive components. This chapter highlights the bioactive composition of mushrooms by relating structure to bioactivity and demonstrating therapeutic effects on some human diseases using existing literature. The potentials of mushrooms or their products for the treatment or management of diseases, such as tropical illnesses and COVID-19 pandemic, among other issues, have been discussed. Chemistry of bioactive compounds, structure–activity relationships, patents, and analyses of data obtained have been reported and studied for interpretation of results.
Pluramycins is the general name of a family of natural products characterized by a common anthrapyranone framework, which is diversely substituted at the C2 and C5 positions and can exhibit a variety of deoxyaminosugars at C8 and C10. Their outstanding biological response towards many afflictions in humans has motivated an extensive study of structure-activity correlations, and at the same time, has encouraged efforts to develop improved total syntheses. The introduction of this review presents a general perspective of the topic, focusing on the structural features of these molecules. Subsequently, the following section summarizes the main range of biological activities exhibited by this group, particularly the antitumor and cytotoxic effects. Finally, the synthesis of these molecules is addressed on two fronts: biosynthetic and synthetic pathways. The last section described the most recent examples found in literature, thus completing the global panorama with which this issue is approached.
The excessive inflammation, oxidative stress, and impaired angiogenesis are major factors leading to difficulties in chronic wound healing. To develop bioactive materials with intrinsic antioxidant and anti-inflammatory properties, we prepared hydrogels for the first time using paramylon secreted by Euglena gracilis which is a polysaccharide has been approved by FDA as food additive. Results showed that the paramylon hydrogel has favourable anti-inflammatory effects and the ability to scavenge reactive oxygen species (ROS) through free radical destruction, deoxygenation, and singlet oxygen quenching, and inhibit ROS production by chelating the metal ions required for the formation of ROS. We found that the paramylon hydrogel could effectively reduce wound inflammation and promote angiogenesis to facilitate wound repair. Furthermore, for the first time, we found that paramylon hydrogel could promote the formation of blood vessels via the HIF-1α-VEGF pathway. These results indicated that the highly bioactive paramylon could be the preferred material for wound healing.
Pleurotus citrinopileatus , the nutritious and palatable edible mushroom, can be taken as an appropriate material to prepare high-grade flavoring agents. Based on this, this study aimed to investigate the feasibility of productive proteases system from Actinomucor elegans to prepare P. citrinopileatus hydrolysate (PCH). The A. elegans crude protease (AECP) was prepared from the solid state fermentation product of P. citrinopileatus by A. elegans . AECP and four commercial proteases (Alcalase, Neutrase, Papain, and Protamex) were applied to acquire five kinds of PCHs respectively. The physical-chemical properties of PCHs as well as its concentration and composition of non-volatile compounds were comparatively analyzed. Electronic tongue was utilized to evaluate sensory characteristics. AECP was found to be the most effective protease with the top hydrolysis degree of 35.91% and protein recovery of 81.46%. The result of molecular weight distribution indicated that below 500 Da peptides were observed to be the main fraction of AECP hydrolysates, meanwhile AECP hydrolysates showed the highest content of MSG-like (20.23 ± 0.16 mg/g) and flavor 5'-nucleotide (4.30 ± 0.07 mg/g). Besides, the AECP hydrolysates exhibited favorable aftertaste-umami, in which peptides below 500 Da showed a higher correlation with aftertaste-umami by results of partial least-squares regression. These results indicated the feasibility for PCHs application as flavor additives or seasoning in food industry. The AECP might be used as an alternative enzyme choice because of its low cost and high hydrolysis efficiency.
Edible fungus polysaccharide (EFP) is mainly extracted from the fruiting body, mycelium and fermentation broth of fungi. As one of the main bioactive components, EFP has potential health promoting effects. Its extracted polysaccharide has biological activities such as enhancing immunity, anti-tumor, anti-radiation, delaying aging and antioxidation. It has been widely used in food, health products, medicine and other industries. The biological activity of EFP is related to its radical group. The isolation, purification and structure identification are the premise of the bioactivity research and application of EFP. At present, the research on polysaccharides and their structures is helpful to guide and develop their pharmacological effects, biological activities and products. This paper reviews the research status of extraction, purification and structure determination of EFP, such as NMR, methylation analysis and some other methods used in carbohydrate chemical characterization. In addition, the research progress of EFP functional activity and its application in other fields were described, so as to provide basis and reference for the further study of EFP.
Pleurotus spp. is one of the most precious and common edible fungi, polysaccharides were the main active component. The structural, biological activities and structure-activity relationship (SAR) of polysaccharides from Pleurotus spp. were systematically reviewed. On the basis of structure and biological activity, structure-activity relationships were also analyzed and discussed to look forward to its future research direction and application prospect. In the past 5 years, about 30 kinds of polysaccharides were isolated from Pleurotus spp., and their preliminary structures were studied, but the fine structures were seldomly reported. The polysaccharides showed the activities of immunomodulatory, hypoglycemic, anti-inflammatory, antioxidant, anti-ageing, hepatoprotective, anti-tumor, hypolipidemic and regulating intestinal flora, but the mechanism was needed further study. There were few studies on the SAR of polysaccharides from Pleurotus, and the polysaccharides of P. eryngii were studied. It was found that the biological activities of polysaccharides were affected by molecular weight, monosaccharide composition, sugar chain structure and configuration. In addition, sulfonation and selenization could significantly increase the bioactivities of polysaccharides. These findings might help to better understand the research status of polysaccharides from Pleurotus spp. and provided a scientific basis for their application as functional foods.
Amomum longiligulare polysaccharides 1 (ALP1) was a glucosan that possessed an immune enhancement ability. However, disadvantages including short biological half-life hindered the application of ALP1. To solve these shortcomings, ALP1 was successfully prepared to nanoparticles (ALPP) with poly (lactic-co-glycolic acid) in the present study. And the optimal preparation conditions were developed by using the response surface method with a Box-Behnken design. The results showed that the encapsulation efficiency of ALPP reached a high level (79.88%) when the volume ratio of the water phase to the organic phase was 1:7, the volume ratio of the primary emulsion to the external water phase was 1:7, and the concentration of F68 was 0.7%. ALPP showed a controlled and sustained release. Meanwhile, the scanning electron microscope results showed that ALPP was a kind of nanoparticles with a diameter of 389.77 nm. In addition, the activating effect of ALPP on macrophages was studied. The results indicated that ALPP showed a better activity on promoting the RAW264.7 cells' activities and polarizing RAW264.7 cells into both M1 type and M2 type macrophages, compared to ALP1.
Edible fungi are large fungi with high added value that can be utilized as resources. They are rich in high-quality protein, carbohydrate, various vitamins, mineral elements and other nutrients, and are characterized by high protein, low sugar, low fat and low cholesterol. In addition, edible fungi contain a variety of bioactive substances, such as polysaccharides, dietary fiber, steroids, polyphenols, and most of these compounds have antioxidant, anti-tumor and other physiological functions. This review comprehensively discusses the bioactive components and functional characteristics of edible fungi (such as antioxidant, anti-aging, hypolipidemic activities, etc.). Then the recent developments and prospect in the high-valued utilization of edible fungi are discussed and summarized. The objective of this review is to improve the understanding of health-promoting properties of edible fungi, and provide reference for the industrial production of edible fungi-based health products.
Lentinus edodes, an important edible mushroom cultivated in East Asia for thousands of years, has been widely used as food and medicinal ingredient worldwide. Modern phytochemistry studies have demonstrated that L. edodes is very rich in bioactive polysaccharides, especially the β-glucans. Over the past two decades, the isolation, chemical properties, and bioactivities of polysaccharides from fruiting bodies, mycelium and fermentation broth of L. edodes have been drawing much attention from scholars around the world. It has been demonstrated that L. edodes polysaccharides possess various remarkable biological activities, including anti-oxidant, anti-tumor, anti-aging, anti-inflammation, immunomodulatory, antiviral, and hepatoprotection effects. This review summarizes the recent development of polysaccharides from L. edodes including the isolation methods, structural features, bioactivities and mechanisms, and their structure-activity relationship, which can provide useful research underpinnings and update information for their further application as therapeutic agents and functional foods.
In this research, a novel polysaccharide (PCP) was extracted from Pleurotus citrinopileatus and purified by Sephadex G-150 gel column, and its antitumor activity was investigated using the model H22 tumor-bearing mice. PCP was found to be composed of arabinose, galactose, glucose, xylose, mannose and glucuronic acid in a proportion of 0.66: 14.59: 10.77: 1: 0.69: 0.23 with average molecular weight of 7.30 × 10⁵ Da. Further analysis suggested that PCP was a pyranose with α-type and β-type glycosidic residues. The antitumor assays in vivo indicated that PCP could effectively suppress H22 solid tumor growth, protect immune organs and improve inflammation and anemia. Besides, Annexin V-FITC/PI double staining and JC-1 staining demonstrated that PCP could induce apoptosis of H22 hepatoma cells. The PI staining assay revealed that PCP induced H22 hepatoma cells apoptosis by arresting cell cycle in S phase. These results suggest that the polysaccharide from Pleurotus citrinopileatus possesses potential value in the treatment of liver cancer.
In the wide field of nutraceuticals, the effects of mushrooms on immunity, cancer and including autoimmunity have been proposed for centuries but in recent years a growing interest has led scientists to elucidate which specific compounds have bioactive properties and through which mechanisms. Glucans and specific proteins are responsible for most of the biological effects of mushrooms, particularly in terms of immunomodulatory and anti-tumor results. Proteins with bioactive effects include lectins, fungal immunomodulatory proteins (FIPs), ribosome inactivating proteins (RIPs), ribonucleases, laccases, among others. At the present status of knowledge, numerous studies have been performed on cell lines and murine models while only a few clinical trials have been conducted. As in most cases of dietary components, the multitude of variables implicated in the final effect and an inadequate standardization are expected to affect the observed differences, thus making the available evidence insufficient to justify the treatment of human diseases with mushrooms extracts. We will herein provide a comprehensive review and critically discussion the biochemical changes induced by different mushroom compounds as observed in in vitro studies, particularly on macrophages, dendritic cells, T cells, and NK cells, compared to in vivo and human studies. Additional effects are represented by lipids which constitute a minor part of mushrooms but may have a role in reducing serum cholesterol levels or phenols acting as antioxidant and reducing agents. Human studies provide a minority of available data, as well illustrated by a placebo-controlled study of athletes treated with β-glucan from Pleurotus ostreatus. Variables influencing study outcomes include different mushrooms strains, growing conditions, developmental stage, part of mushroom used, extraction method, and storage conditions. We foresee that future rigorous research will be needed to determine the potential of mushroom compounds for human health to reproduce the effects of some compounds such as lentinan which a metaanalysis demonstrated to increase the efficacy of chemotherapy in the treatment of lung cancer and in the improvement of the patients quality of life.
Pleurotus citrinopileatus(P. citrinopileatus) is a precious medicinal fungus. A novel polysaccharide (CMP) was separated from the mycelia of P. citrinopileatus. The CMP is a neutral polysaccharide with Mw of 3.22×10⁶ Da. The CMP is composed of D-Mannose, D-Glucose and D-Galactose with molar ratio of 0.33:1.03:0.21. The backbone of CMP is composed of →3)-α-D-Glcp-(1→ and →3, 6)-α-D-Glcp-(1→, while branches contain →3)-α-D-Manp-(1→ and →3)-β-D-Galp-(1→. The surface morphology of CMP is smooth with irregular fragmented structure. The IC50 value of CMP is 0.371 mg/mL. Compared with acarbose (0.289 mg/mL), it suggest that CMP has effectively inhibition on α-glucosidase and the inhibition type is Mixed Type inhibition. The CMP can significantly promote the uptake of glucose and the synthesis of glycogen to regulate the insulin resistance of HepG2 insulin resistance cells (HepG2-IR). The regulation of insulin resistance in HepG2-IR cells by CMP is through Pi3K/Akt pathway. The manuscript provide the alternative of polysaccharides from P. citrinopileatus fruiting bodies and develop new substance for hypoglycemic food.
The extracellular polysaccharides are important biological resources with wide application. Pleurotus citrinopileatus(P. citrinopileatus) is a precious medicinal fungus with variously bioactivity. The literatures on the specific components with hypoglycemic effect in crude polysaccharides from fermented broth of P. citrinopileatus and the structure have not been reported. A novel acid polysaccharide (CFP) with Mw of 1.062 × 10⁶ Da was isolated from fermented broth of P. citrinopileatus. The hypoglycemic activity in vitro of CFP and accurately chemical structure were explored. The CFP had effectively inhibition on α-glucosidase with IC50 values of 0.556 mg/mL through non-competitive inhibition. The CFP had no effect on normal growth and proliferation of HepG2 cells but can regulate the insulin resistance in HepG2-IR cells. Simultaneously, the CFP can significantly reduce the oxidative stress in HepG2-IR cells. All the results elucidated that CFP had effective hypoglycemic activity. The structural characterization revealed that CFP was composed of D-Gal, D-Glc, D-GalA and D-GlcA with a percentage of 20.53:28.75:5.55:45.17. The backbone of CFP was composed of →3)-α-D-Glcp-(1→, →3)-α-D-GlcAp-(1→ and →3, 6)-α-D-Glcp-(1→, while branches contained →3)-β-D-GalAp-(1→ and →3)-β-D-Galp-(1 → . The CFP had triple-helix conformation. The surface of CFP was rough and had irregular small fragments with hole-like and stripe-like structure. The manuscript further identified the main carbohydrates components in the fermentation liquid of P. citrinopileatus. It provided basis for the development and utilization of active components in P. citrinopileatus. The structural characterization of polysaccharide can provide experimental basis for exploration of structure-activity relationship.
Human peripheral-blood monocytes are used as an established in vitro system for generating macrophages. For several reasons, monocytic cell lines such as THP-1 have been considered as a possible alternative. In view of their distinct developmental origins and phenotypic attributes, we set out to assess the extent to which human monocyte-derived macrophages (MDMs) and phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells were overlapping across a variety of responses to activating stimuli. Resting (M0) macrophages were polarized toward M1 or M2 phenotypes by 48-h incubation with LPS (1 μg/ml) and IFN-γ (10 ng/ml) or with IL-4 (20 ng/ml) and IL-13 (5 ng/ml), respectively. At the end of stimulation, MDMs displayed more pronounced changes in marker gene expression than THP-1. Upon assaying an array of 41 cytokines, chemokines and growth factors in conditioned media (CM) using the Luminex technology, secretion of 29 out of the 41 proteins was affected by polarized activation. While in 12 of them THP-1 and MDM showed comparable trends, for the remaining 17 proteins their responses to activating stimuli did markedly differ. Quantitative comparison for selected analytes confirmed this pattern. In terms of phenotypic activation markers, measured by flow cytometry, M1 response was similar but the established MDM M2 marker CD163 was undetectable in THP-1 cells. In a beads-based assay, MDM activation did not induce significant changes, whereas M2 activation of THP-1 decreased phagocytic activity compared to M0 and M1. In further biological activity tests, both MDM and THP-1 CM failed to affect proliferation of mouse myogenic progenitors, whereas they both reduced adipogenic differentiation of mouse fibro-adipogenic progenitor cells (M2 to a lesser extent than M1 and M0). Finally, migration of human umbilical vein endothelial cells was enhanced by CM irrespective of cell type and activation state except for M0 CM from MDMs. In summary, PMA-differentiated THP-1 macrophages did not entirely reproduce the response spectrum of primary MDMs to activating stimuli. We suggest that THP-1 be regarded as a simplified model of human macrophages when investigating relatively straightforward biological processes, such as polarization and its functional implications, but not as an alternative source in more comprehensive immunopharmacology and drug screening programs.
PCPS from P. citrinopileatus mushroom extract is a β -1,6-glucan possessing a proinflammatory effect on innate immune cells. The PCPS stimulated THP-1 macrophages to secrete significant levels of TNF. Moreover, the mRNA expressions of TNF and IL-1 β were significantly enhanced by PCPS treatment. However, the PCPS did not induce to express both IL-12 and IL-10 mRNA in the macrophages. Next, the P. cornucopiae extract (containing mainly PCPS) treatment against mice showed significant increases in TNF and IL-1 β mRNA expressions in the peritoneal macrophages of them. In this study, the expression levels of IFN γ mRNA in the spleen were almost the same between the extract- (PCPS-) treated group and control group. However, the expression of IL-4 mRNA showed a lower level in the extract-treated group than that in the control. Our results suggested that the PCPS could induce proinflammatory action in the immune response. In addition, the proinflammatory effect of the PCPS on THP-1 was enhanced by 5′-GMP-Na, while it was reduced by vitamin D 2 . These two compounds are majorly contained in the P. citrinopileatus mushroom. Therefore, these results suggested that the P. citrinopileatus mushroom might contain other immune regulative compounds, such as vitamin D 2 , as well as PCPS.
Helminths have strong immunoregulatory properties that may be exploited in treatment of chronic immune disorders, such as multiple sclerosis and inflammatory bowel disease. Essential players in the pathogenesis of these diseases are proinflammatory macrophages. We present evidence that helminths modulate the function and phenotype of these innate immune cells. We found that soluble products derived from theTrichuris suis(TsSP) significantly affect the differentiation of monocytes into macrophages and their subsequent polarization. TsSPs reduce the expression and production of inflammatory cytokines, including IL-6 and TNF, in human proinflammatory M1 macrophages. TsSPs induce a concomitant anti-inflammatory M2 signature, with increased IL-10 production. Furthermore, they suppress CHIT activity and enhance secretion of matrix metalloproteinase 9. Short-term triggering of monocytes with TsSPs early during monocyte-to-macrophage differentiation imprinted these phenotypic alterations, suggesting long-lasting epigenetic changes. The TsSP-induced effects in M1 macrophages were completely reversed by inhibiting histone deacetylases, which corresponded with decreased histone acetylation at theTNF and IL6 promoters. These results demonstrate that TsSPs have a potent and sustained immunomodulatory effect on human macrophage differentiation and polarization through epigenetic remodeling and provide new insights into the mechanisms by which helminths modulate human immune responses.
The molecular and cellular mechanisms that underlie the many roles of macrophages in health and disease states in vivo remain poorly understood. The purpose of this Review is to present and discuss current knowledge on the developmental biology of macrophages, as it underlies the concept of a layered myeloid system composed of 'resident' macrophages that originate mainly from progenitor cells generated in the yolk sac and of 'passenger' or 'transitory' myeloid cells that originate and renew from bone marrow hematopoietic stem cells, and to provide a framework for investigating the functions of macrophages in vivo.
Monocytes and macrophages have crucial and distinct roles in tissue homeostasis and immunity, but they also contribute to a broad spectrum of pathologies and are thus attractive therapeutic targets. Potential intervention strategies that aim to manipulate these cells will require an in-depth understanding of their origins and the mechanisms that ensure their homeostasis. Recent evidence shows that monocytes do not substantially contribute to most tissue macrophage populations in the steady state or during certain types of inflammation. Rather, most tissue macrophage populations in mice are derived from embryonic precursors, are seeded before birth and can maintain themselves in adults by self-renewal. In this Review, we discuss the evidence that has dramatically changed our understanding of monocyte and macrophage development, and the maintenance of these cells in the steady state.
The CCL2 chemokine mediates monocyte egress from bone marrow and recruitment into inflamed tissues through interaction with the CCR2 chemokine receptor, and its expression is upregulated by proinflammatory cytokines. Analysis of the gene expression profile in GM-CSF- and M-CSF-polarized macrophages revealed that a high CCL2 expression characterizes macrophages generated under the influence of M-CSF, whereas CCR2 is expressed only by GM-CSF-polarized macrophages. Analysis of the factors responsible for this differential expression identified activin A as a critical factor controlling the expression of the CCL2/CCR2 pair in macrophages, as activin A increased CCR2 expression but inhibited the acquisition of CCL2 expression by M-CSF-polarized macrophages. CCL2 and CCR2 were found to determine the extent of macrophage polarization because CCL2 enhances the LPS-induced production of IL-10, whereas CCL2 blockade leads to enhanced expression of M1 polarization-associated genes and cytokines, and diminished expression of M2-associated markers in human macrophages. Along the same line, Ccr2-deficient bone marrow-derived murine macrophages displayed an M1-skewed polarization profile at the transcriptomic level and exhibited a significantly higher expression of proinflammatory cytokines (TNF-α, IL-6) in response to LPS. Therefore, the CCL2-CCR2 axis regulates macrophage polarization by influencing the expression of functionally relevant and polarization-associated genes and downmodulating proinflammatory cytokine production.
Mushroom polysaccharides have traditionally been used for the prevention and treatment of a multitude of disorders like infectious illnesses, cancers and various autoimmune diseases. Crude mushroom extracts have been tested without detailed chemical analyses of its polysaccharide content. For the present study we decided to chemically determine the carbohydrate composition of semi-purified extracts from 2 closely related and well known basidiomycete species, i.e. Agaricus bisporus and A. brasiliensis and to study their effects on the innate immune system, in particular on the in vitro induction of pro-inflammatory cytokines, using THP-1 cells.
Mushroom polysaccharide extracts were prepared by hot water extraction and precipitation with ethanol. Their composition was analyzed by GC-MS and NMR spectroscopy. PMA activated THP-1 cells were treated with the extracts under different conditions and the production of pro-inflammatory cytokines was evaluated by qPCR.
Semi-purified polysaccharide extracts of A. bisporus and A. brasiliensis (= blazei) were found to contain (1→6),(1→4)-linked α-glucan, (1→6)-linked β-glucan, and mannogalactan. Their proportions were determined by integration of 1H-NMR signs, and were considerably different for the two species. A. brasiliensis showed a higher content of β-glucan, while A. bisporus presented mannogalactan as its main polysaccharide. The extracts induced a comparable increase of transcription of the pro-inflammatory cytokine genes IL-1β and TNF-α as well as of COX-2 in PMA differentiated THP-1 cells. Pro-inflammatory effects of bacterial LPS in this assay could be reduced significantly by the simultaneous addition of A. brasiliensis extract.
The polysaccharide preparations from the closely related species A. bisporus and A. brasiliensis show major differences in composition: A. bisporus shows high mannogalactan content whereas A. brasiliensis has mostly β-glucan. Semi-purified polysaccharide extracts from both Agaricus species stimulated the production of pro-inflammatory cytokines and enzymes, while the polysaccharide extract of A. brasiliensis reduced synthesis of these cytokines induced by LPS, suggesting programmable immunomodulation.
Macrophages are ubiquitous in the stromal compartment of tissues under normal physiological conditions and the number of these cells increases markedly with the onset and progression of many pathological states. The mechanisms underlying this response are well described in such conditions as wound healing and malignant tumors, where tissue-specific signals enhance the extravasation of blood monocytes and their subsequent differentiation into macrophages. Recent evidence suggests that macrophages may also be stimulated by microenvironmental factors present in diseased tissues to perform distinct, tissue-specific activities. One such factor, hypoxia (low oxygen tension), results from insufficient vascular perfusion of a given tissue. Various studies have shown that experimental hypoxia alters the morphology, expression of cell surface markers, viability, phagocytosis, metabolic activity, and release of cytokines by macrophages. Here we review the evidence for these macrophage responses to hypoxia, the involvement of co-stimuli, and their implications for the role of macrophages in various disease processes. Because the intracellular mechanisms mediating the effects of hypoxia on gene expression in other cell types have been characterized recently, we discuss their possible involvement in the effects of hypoxia on gene expression in macrophages.
Development of Myeloid Immune Cells
As leukocytes develop to maturity, they proceed through an array of phenotypically distinct intermediates. For T and B lymphocyte populations, the different developmental stages, anatomical locations, and cell signals required for progression are well established. However, until recently, much less has been known about how development proceeds in the myeloid lineage, which includes monocytes, macrophages, and dendritic cells. Geissmann et al. (p. 656 ) review our current understanding of myeloid lineage development and describe the developmental pathways and cues that drive differentiation.
Chemokines constitute a family of chemoattractant cytokines and are subdivided into four families on the basis of the number and spacing of the conserved cysteine residues in the N-terminus of the protein. Chemokines play a major role in selectively recruiting monocytes, neutrophils, and lymphocytes, as well as in inducing chemotaxis through the activation of G-protein-coupled receptors. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages. Both CCL2 and its receptor CCR2 have been demonstrated to be induced and involved in various diseases. Migration of monocytes from the blood stream across the vascular endothelium is required for routine immunological surveillance of tissues, as well as in response to inflammation. This review will discuss these biological processes and the structure and function of CCL2.
Converging studies have shown that M1 and M2 macrophages are functionally polarized in response to microorganisms and host mediators. Gene expression profiling of macrophages reveals that various Gram-negative and Gram-positive bacteria induce the transcriptional activity of a "common host response," which includes genes belonging to the M1 program. However, excessive or prolonged M1 polarization can lead to tissue injury and contribute to pathogenesis. The so-called M2 macrophages play a critical role in the resolution of inflammation by producing anti-inflammatory mediators. These M2 cells cover a continuum of cells with different phenotypic and functional properties. In addition, some bacterial pathogens induce specific M2 programs in macrophages. In this review, we discuss the relevance of macrophage polarization in three domains of infectious diseases: resistance to infection, infectious pathogenesis, and chronic evolution of infectious diseases.
Activated T lymphocytes differentiate into effector cells tailored to meet disparate challenges to host integrity. For example, type 1 and type 2 helper (T(H)1 and T(H)2) cells secrete cytokines that enhance cell-mediated and humoral immunity, respectively. The chemokine monocyte chemoattractant protein-1 (MCP-1) can stimulate interleukin-4 production and its overexpression is associated with defects in cell-mediated immunity, indicating that it might be involved in T(H)2 polarization. Here we show that MCP-1-deficient mice are unable to mount T(H)2 responses. Lymph node cells from immunized MCP-1(-/-) mice synthesize extremely low levels of interleukin-4, interleukin-5 and interleukin-10, but normal amounts of interferon-gamma and interleukin-2. Consequently, these mice do not accomplish the immunoglobulin subclass switch that is characteristic of T(H)2 responses and are resistant to Leishmania major. These effects are direct rather than due to abnormal cell migration, because the trafficking of naive T cells is undisturbed in MCP-1(-/-) mice despite the presence of MCP-1-expressing cells in secondary lymphoid organs of wild-type mice. Thus, MCP-1 influences both innate immunity, through effects on monocytes, and adaptive immunity, through control of T helper cell polarization.
Glucans are (1-3)-beta-D-linked polymers of glucose that are produced as fungal cell wall constituents and are also released into the extracellular milieu. Glucans modulate immune function via macrophage participation. The first step in macrophage activation by (1-3)-beta-D-glucans is thought to be the binding of the polymer to specific macrophage receptors. We examined the binding/uptake of a variety of water soluble (1-3)-beta-D-glucans and control polymers with different physicochemical properties to investigate the relationship between polymer structure and receptor binding in the CR3- human promonocytic cell line, U937. We observed that the U937 receptors were specific for (1-->3)-beta-D-glucan binding, since mannan, dextran, or barley glucan did not bind. Scleroglucan exhibited the highest binding affinity with an IC(50)of 23 nM, three orders of magnitude greater than the other (1-->3)-beta-D-glucan polymers examined. The rank order competitive binding affinities for the glucan polymers were scleroglucan>schizophyllan > laminarin > glucan phosphate > glucan sulfate. Scleroglucan also exhibited a triple helical solution structure (nu = 1.82, beta = 0.8). There were two different binding/uptake sites on U937 cells. Glucan phosphate and schizophyllan interacted nonselectively with the two sites. Scleroglucan and glucan sulfate interacted preferentially with one site, while laminarin interacted preferentially with the other site. These data indicate that U937 cells have at least two non-CR3 receptor(s) which specifically interact with (1-->3)-beta-D-glucans and that the triple helical solution conformation, molecular weight and charge of the glucan polymer may be important determinants in receptor ligand interaction.
We recently identified dectin-1 (betaGR) as a major beta-glucan receptor on leukocytes and demonstrated that it played a significant role in the non-opsonic recognition of soluble and particulate beta-glucans. Using a novel mAb (2A11) raised against betaGR, we show here that the receptor is not dendritic cell-restricted as first reported, but is broadly expressed, with highest surface expression on populations of myeloid cells (monocyte/macrophage (Mphi) and neutrophil lineages). Dendritic cells and a subpopulation of T cells also expressed the betaGR, but at lower levels. Alveolar Mphi, like inflammatory Mphi, exhibited the highest surface expression of betaGR, indicative of a role for this receptor in immune surveillance. In contrast, resident peritoneal Mphi expressed much lower levels of betaGR on the cell surface. Characterization of the nonopsonic recognition of zymosan by resident peritoneal Mphi suggested the existence of an additional beta-glucan-independent mechanism of zymosan binding that was not observed on elicited or bone marrow-derived Mphi. Although this recognition could be inhibited by mannan, we were able to exclude involvement of the Mphi mannose receptor and complement receptor 3 in this process. These observations imply the existence of an additional mannan-dependent receptor involved in the recognition of zymosan by resident peritoneal Mphi.
Toll-like receptors (TLRs) mediate recognition of a wide range of microbial products including lipopolysaccharides, lipoproteins, flagellin, and bacterial DNA, and signaling through TLRs leads to the production of inflammatory mediators. In addition to TLRs, many other surface receptors have been proposed to participate in innate immunity and microbial recognition, and signaling through some of these receptors is likely to cooperate with TLR signaling in defining inflammatory responses. In this report we have examined how dectin-1, a lectin family receptor for beta-glucans, collaborates with TLRs in recognizing microbes. Dectin-1, which is expressed at low levels on macrophages and high levels on dendritic cells, contains an immunoreceptor tyrosine-based activation motif-like signaling motif that is tyrosine phosphorylated upon activation. The receptor is recruited to phagosomes containing zymosan particles but not to phagosomes containing immunoglobulin G-opsonized particles. Dectin-1 expression enhances TLR-mediated activation of nuclear factor kappa B by beta-glucan-containing particles, and in macrophages and dendritic cells dectin-1 and TLRs are synergistic in mediating production of cytokines such as interleukin 12 and tumor necrosis factor alpha. Additionally, dectin-1 triggers production of reactive oxygen species, an inflammatory response that is primed by TLR activation. The data demonstrate that collaborative recognition of distinct microbial components by different classes of innate immune receptors is crucial in orchestrating inflammatory responses.
Pattern-recognition receptors (PRRs) initiate innate immunity through pathogen recognition. Serum PRRs opsonize pathogens for enhanced phagocytic clearance. Toll-like receptors (TLRs) initiate common NF-kappaB/AP-1 and distinct IRF3/7 pathways to coordinate innate immunity and to initiate adaptive immunity against diverse pathogens. Cytoplasmic caspase-recruiting domain (CARD) helicases, such as RIG-I/MDA5, mediate antiviral immunity by inducing the production of type I interferons via the adaptor IPS-1, whereas nucleotide-binding oligomerization domain (NOD)-like receptors mediate mainly antibacterial immunity by activating NF-kappaB or inflammasomes. Dectin-1 is important for antifungal immunity, promoting phagocytosis and activating NF-kappaB. Potentially harmful TLR signaling pathways can be negatively regulated by negative feedback mechanisms and also by anti-inflammatory factors such as TGFbeta, interleukin (IL)-10, and steroids. Many combinations of TLR-TLR and TLR-NOD modulate inflammatory responses. TLRs and NALP3 interplay to produce mature IL-1beta. Thus signaling pathways downstream of PRRs and their cross talk control immune responses in effective manners.
Macrophages (Mφ) undergo activation to pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes in response to pathophysiologic stimuli and dysregulation of the M1-M2 balance is often associated with diseases. Therefore, studying mechanisms of macrophage polarization may reveal new drug targets. Human Mφ polarization is generally studied in primary monocyte-derived Mφ (PBMC Mφ) and THP-1-derived Mφ (THP-1 Mφ). We compared the polarization profile of THP-1 Mφ with that of PBMC Mφ to assess the alternative use of THP-1 for polarization studies. Cellular morphology, the expression profiles of 18 genes and 4 cell surface proteins, and phagocytosis capacity for apoptotic cells and S. aureus bioparticles were compared between these Mφ, activated towards M1, M2a, or M2c subsets by stimulation with LPS/IFNγ, IL-4, or IL-10, respectively, for 6 h, 24 h and 48 h. The Mφ types are unique in morphology and basal expression of polarization marker genes, particularly CCL22, in a pre-polarized state, and were differentially sensitive to polarization stimuli. Generally, M1 markers were instantly induced and gradually decreased, while M2 markers were markedly expressed at a later time. Expression profiles of M1 markers were similar between the polarized Mφ types, but M2a cell surface markers demonstrated an IL-4-dependent upregulation only in PBMC Mφ. Polarized THP-1 Mφ but not PBMC Mφ showed distinctive phagocytic capacity for apoptotic cells and bacterial antigens, respectively. In conclusion, our data suggest that THP-1 may be useful for performing studies involving phagocytosis and M1 polarization, rather than M2 polarization.
Obesity is associated with chronic low-grade inflammation of adipose tissue (AT) and an increase of AT macrophages (ATMs) that is linked to the onset of type 2 diabetes. We have recently shown that focal sites of inflammation around dying adipocytes, so-called crown-like structures, exhibit a unique microenvironment for macrophage proliferation. Interestingly, locally proliferating macrophages were not classically activated (M1), but they exhibited a rather alternatively activated (M2) immune phenotype. In this study, we established organotypic cell cultures of AT explants to study the impact of cytokine treatment on local ATM proliferation, without the bias of early monocyte recruitment. We show that exposure of AT to Th2 cytokines, such as IL-4, IL-13, and GM-CSF, stimulates ATM proliferation, whereas Th1 cytokines, such as TNF-α, inhibit local ATM proliferation. Furthermore, AT from obese mice exhibits an increased sensitivity to IL-4 stimulation, indicated by an increased phosphorylation of STAT6. In line with this, gene expression of the IL-4 receptor (Il4ra) and its ligand IL-13 are elevated in AT of obese C57BL/6 mice. Most importantly, Il4ra expression and susceptibility to IL-4 or IL-13 treatment depend on IL-6 signaling, which seems to be the underlying mechanism of local ATM proliferation in obesity. We conclude that IL-6 acts as a Th2 cytokine in obesity by stimulating M2 polarization and local ATM proliferation, presumably due to upregulation of the IL-4 receptor α.
Many edible mushrooms have become attractive as “health foods” and as source materials for immunomodulators. To increase our insight in the immune-modulatory properties of a polysaccharide of the oyster mushroom Pleurotus citrinopileatus, PCPS, we analyzed its effects on the function of human dendritic cells (DCs). We showed that PCPS induces upregulation of the surface maturation markers CD80, CD86 and HLA-DR on DCs, indicating its potential to induce DC maturation. In addition, PCPS stimulates DCs to secrete the pro-inflammatory cytokines TNF, IL-1β, IL-6 and IL-12, as well as the anti-inflammatory cytokine IL-10, and induces enhanced mRNA levels of the chemokines CCL2, CCL3, CCL8, CXCL9, CXCL10, and LTA. The secretion of TNF and IL-12 by PCPS-activated DCs could significantly be decreased by an anti-Dectin-1 antibody, as well as by a Syk kinase and a Raf-1 inhibitor, indicating that PCPS induces Dectin-1 signaling at least partly through the Syk- and the Raf-1-dependent pathways in DCs. Structural analysis of PCPS suggests that this polysaccharide is a β-1,3-branched β-1,6-glucan, which is in line with its capacity to activate Dectin-1. We showed that PCPS can induce TLR2 and TLR4, but not TLR3, signaling using TLR-HEK293 reporter cell lines. In human DCs, the effect of PCPS was additively increased by TLR4 activation, and synergistically enhanced by stimulation of TLR2, suggesting that interaction of PCPS with these TLRs contributes to the observed DC modulation. In conclusion, PCPS has the capacity to activate human DCs via multiple pathways.
Background:
The role of glucan in stimulation of immune reactions has been studied for several decades. In this report, we focused on the effects of orally administered glucan Maitake and Shiitake on immune reactions.
Materials and methods:
We measured phagocytosis, NK cell activity, and secretion of IL-6, IL-12, IFN-γ as well as C-reactive protein (CRP) after 14 days of oral application of tested glucans. For comparison, active hexose correlated compound (AHCC) was used in all reactions.
Results:
We found significant stimulation of defense reaction. In all cases, the most active was the Maitake-Shiitake combination, with Maitake alone being the second strongest, followed by Shiitake on its own and AHCC.
Conclusions:
Short-term oral application of natural immunomodulating glucans from Maitake and Shiitake mushrooms strongly stimulated both the cellular and humoral branch of immune reactions. These activities were significantly higher than those of AHCC.
Tissue-resident macrophages are highly heterogeneous in terms of their functions and phenotypes as a consequence of adaptation to different tissue environments. Local tissue-derived signals are thought to control functional polarization of resident macrophages; however, the identity of these signals remains largely unknown. It is also unknown whether functional heterogeneity is a result of irreversible lineage-specific differentiation or a consequence of continuous but reversible induction of diverse functional programs. Here, we identified retinoic acid as a signal that induces tissue-specific localization and functional polarization of peritoneal macrophages through the reversible induction of transcription factor GATA6. We further found that GATA6 in macrophages regulates gut IgA production through peritoneal B-1 cells. These results provide insight into the regulation of tissue-resident macrophage functional specialization by tissue-derived signals.
It is thought that monocytes rapidly differentiate to macrophages or dendritic cells (DCs) upon leaving blood. Here we have shown that Ly-6C(+) monocytes constitutively trafficked into skin, lung, and lymph nodes (LNs). Entry was unaffected in gnotobiotic mice. Monocytes in resting lung and LN had similar gene expression profiles to blood monocytes but elevated transcripts of a limited number of genes including cyclo-oxygenase-2 (COX-2) and major histocompatibility complex class II (MHCII), induced by monocyte interaction with endothelium. Parabiosis, bromodoxyuridine (BrdU) pulse-chase analysis, and intranasal instillation of tracers indicated that instead of contributing to resident macrophages in the lung, recruited endogenous monocytes acquired antigen for carriage to draining LNs, a function redundant with DCs though differentiation to DCs did not occur. Thus, monocytes can enter steady-state nonlymphoid organs and recirculate to LNs without differentiation to macrophages or DCs, revising a long-held view that monocytes become tissue-resident macrophages by default.
The hot water soluble extract of Pleurotus citrinopileatus (HWE-P) induced high expression of mRNA of tumor necrosis factor (TNF)-α, which is a proinflammatory cytokine, in the stimulated murine macrophage RAW264. However, unlike lipopolysaccharides (LPS), the extract did not induce the expression of mRNA in other cytokines, such as in IL-12 and IL-10. TNF-α production, which was induced from RAW264 stimulated with HWE-P (1 mg·mL-1), was approximately 400 pg·mL-1. These findings showed that the fruiting body of P. citrinopileatus stimulated an early immunological response of a murine macrophage. Furthermore, we chromatographically separated and purified an active fraction from the crude extract of P. citrinopileatus and measured its immunomodulating activity in cytokine production from the stimulated macrophages. This crude extract was separated into six fractions (HWE-P-I, II, III, IV, V, and VI) by anion exchange chromatography using DEAE-Sepharose gel. Then it was found that the HWE-P-IV fraction, which possessed a molecular mass approximately 450 kDa, showed the strongest immunomodulating activity in TNF-α production (4.9 ng·mL-1) from the macrophages. This fraction was mainly composed of a sugar. Moreover, production of nitric oxide (NO) was detected in the macrophages stimulated with this fraction. The amount of NO produced from stimulated RAW264 was 33.8 μM. These results indicate that a polysaccharide fraction from P. citrinopileatus possesses a potent immunomodulating activity. Thus, this culinary-medicinal species could become an effective component of a functional food.
Medicinal health benefits uses of edible as well as non-edible mushrooms have been long recognized. The pharmacological potential of mushrooms, especially antitumor, immunostimulatory and anti-inflammatory activities has been documented. Wild ectomycorrhizal mushroom, Lactarius rufus had the anti-inflammatory and antinociceptive potential of their polysaccharides evaluated using the formalin model. Two structurally different (1→3),(1→6)-linked β-d-glucans were isolated from fruiting bodies. Soluble (FSHW) β-d-glucan 1-30mgkg(-1) produced potent inhibition of inflammatory pain caused by formalin when compared with the insoluble one (IHW), suggesting that solubility and/or branching degree could alter the activity of β-glucans. Their structures were determined using mono- and bi-dimensional NMR spectroscopy, methylation analysis, and controlled Smith degradation. They were β-d-glucans, with a main chain of (1→3)-linked Glcp residues, substituted at O-6 by single-unit Glcp side chains (IHW), on average to every fourth residue of the backbone, or by mono- and few oligosaccharide side chains for soluble β-glucan.
Human monocyte-derived dendritic cells (DCs) show remarkable phenotypic changes upon direct contact with soluble products (SPs) of Trichuris suis, a pig whipworm that is experimentally used in therapies to ameliorate inflammation in patients with Crohn's disease and multiple sclerosis. These changes may contribute to the observed induction of a T helper 2 (Th2) response and the suppression of Toll-like receptor (TLR)-induced Th1 and Th17 responses by human DCs primed with T. suis SPs. Here it is demonstrated that glycans of T. suis SPs contribute significantly to the suppression of the LPS-induced expression in DCs of a broad variety of cytokines and chemokines, including important pro-inflammatory mediators such as TNF-α, IL-6, IL-12, LTA, CCL2, CXCL9 and CXCL10. In addition, the data show that human DCs strongly bind T. suis SP-glycans via the C-type lectin receptors (CLRs) mannose receptor (MR) and DC-specific ICAM-3-grabbing non-integrin (DC-SIGN). The interaction of DCs with T. suis glycans likely involves mannose-type glycans, rather than fucosylated glycans, which differs from DC binding to soluble egg antigens of the human worm parasite, Schistosoma mansoni. In addition, macrophage galactose-type lectin (MGL) recognizes T. suis SPs, which may contribute to the interaction with immature DCs or other MGL-expressing immune cells such as macrophages. The interaction of T. suis glycans with CLRs of human DCs may be essential for the ability of T. suis to suppress a pro-inflammatory phenotype of human DCs. The finding that the T. suis-induced modulation of human DC function is glycan-mediated is novel and indicates that helminth glycans contribute to the dampening of inflammation in a wide range of human inflammatory diseases.
Ly6C(hi) monocytes seed the healthy intestinal lamina propria to give rise to resident CX(3)CR1(+) macrophages that contribute to the maintenance of gut homeostasis. Here we report on two alternative monocyte fates in the inflamed colon. We showed that CCR2 expression is essential to the recruitment of Ly6C(hi) monocytes to the inflamed gut to become the dominant mononuclear cell type in the lamina propria during settings of acute colitis. In the inflammatory microenvironment, monocytes upregulated TLR2 and NOD2, rendering them responsive to bacterial products to become proinflammatory effector cells. Ablation of Ly6C(hi) monocytes ameliorated acute gut inflammation. With time, monocytes differentiated into migratory antigen-presenting cells capable of priming naive T cells, thus acquiring hallmarks reminiscent of dendritic cells. Collectively, our results highlight cellular dynamics in the inflamed colon and the plasticity of Ly6C(hi) monocytes, marking them as potential targets for inflammatory bowel disease (IBD) therapy.
MD-Fraction, a highly purified, soluble β-(1,3) (1,6)-glucan obtained from Grifola frondosa (an oriental edible mushroom), has been reported to inhibit tumor growth by modulating host immunity. β-Glucan, a major component of the fungal cell wall, is generally recognized by PRRs expressed on macrophages and DCs, such as Dectin-1, and the ability of β-glucans to modulate host immunity is influenced by their structure and purity. Most cellular studies have used particulate β-glucans, such as yeast zymosan (crude β-glucan) and curdlan (purified β-glucan). However, little is known about the cellular mechanism of soluble β-glucans, including MD-Fraction, despite significant therapeutic implications. In this study, we investigated the cellular mechanism of MD-Fraction in murine resident macrophages and compared it with two well-known β-glucan particles. MD-Fraction induced GM-CSF production rapidly through Dectin-1-independent ERK and p38 MAPK activation. Subsequently, MD-Fraction-induced GM-CSF enhanced proliferation and Dectin-1 expression, which permitted Dectin-1-mediated TNF-α induction through the Syk pathway. Curdlan induced not only the proliferation and activation of Dectin-1/Syk signaling in a manner similar to MD-Fraction but also the uncontrolled, proinflammatory cytokine response. Contrastingly, zymosan reduced proliferation and Dectin-1 expression significantly, indicating that the mechanism of macrophage activation by MD-Fraction differs from that of zymosan. This is the first study to demonstrate that purified β-glucans, such as MD-Fraction and curdlan, induce GM-CSF production directly, resulting in Dectin-1/Syk activation in resident macrophages. In conclusion, we demonstrated that MD-Fraction induces cell proliferation and cytokine production without excessive inflammation in resident macrophages, supporting its immunotherapeutic potential.
In schistosomiasis, a major human parasitic disease caused by helminths, different life-stages of the parasite contribute to the developing host immune response. To increase our understanding of the mechanisms that play a role in shaping the host immune responses, we have investigated the effects of schistosome glycoconjugates on the phenotype of dendritic cells (DCs), which form a crucial link between the innate and the adaptive immunity. We show here that Schistosoma mansoni worm glycolipids induce DC activation as indicated by upregulation of the maturation markers CD80, CD86 and MHC-II, as well as the production of the cytokines interleukin-12 p40 (IL-12 p40), IL-10, IL-1beta, IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha). Co-culture of glycolipid-primed DCs with naïve T cells results in skewing of the T cell response towards a Th1 profile. Remarkably, the DC activation is dependent on fucosylated glycan moieties of the glycolipids. On the DCs, the C-type lectin DC-SIGN and TLR4 are both critically involved in the induced activation, as was demonstrated by using monoclonal antibodies that block interaction of these receptors with the glycolipids. Furthermore, whereas the worm glycolipids were not able to activate HEK 293 cells expressing TLR4, they did show TLR4 activation after introduction of DC-SIGN in the HEK 293-TLR4 cells. Our data provide evidence for a novel function of DC-SIGN as an essential co-receptor for TLR4-induced activation of human DCs. This mechanism of TLR4 activation by worm glycolipids may contribute to eliciting Th1 immune responses in schistosome infection.
Dendritic cells (DC) are special subsets of antigen presenting cells characterized by their potent capacity to activate immunologically naive T cells. By subtracting the mRNAs expressed by the mouse epidermus-derived DC line XS52 with the mRNAs expressed by the J774 macrophage line, we identified five novel genes that were expressed selectively by this DC line. One of these genes encoded a type II membrane-integrated polypeptide of 244 amino acids containing a putative carbohydrate recognition domain motif at the COOH-terminal end. This molecule, termed "dectin-1," was expressed abundantly at both mRNA and protein levels by the XS52 DC line, but not by non-DC lines (including the J774 macrophage line). Dectin-1 mRNA was detected predominantly in spleen and thymus (by Northern blotting) and in skin-resident DC, i.e. Langerhans cells (by reverse transcription-polymerase chain reaction). Affinity-purified antibody against dectin-1 identified a 43-kDa glycoprotein in membrane fractions isolated from the XS52 DC line and from the dectin-1 cDNA-transfected COS-1 cells. His-tagged recombinant proteins containing the extracellular domains of dectin-1 showed marked and specific binding to the surface of T cells and promoted their proliferation in the presence of anti-CD3 monoclonal antibody at suboptimal concentrations. These in vitro results suggest that dectin-1 on DC may bind to as yet undefined ligand(s) on T cells, thereby delivering T cell co-stimulatory signals. Not only do these results document the efficacy of subtractive cDNA cloning for the identification of unique genes expressed by DC, they also provide a framework for studying the physiological function of dectin-1.
The carbohydrate polymers known as beta-1,3-d-glucans exert potent effects on the immune system - stimulating antitumour and antimicrobial activity, for example - by binding to receptors on macrophages and other white blood cells and activating them. Although beta-glucans are known to bind to receptors, such as complement receptor 3 (ref. 1), there is evidence that another beta-glucan receptor is present on macrophages. Here we identify this unknown receptor as dectin-1 (ref. 2), a finding that provides new insights into the innate immune recognition of beta-glucans.
Macrophage plasticity and polarization: in vivo veritas
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