Birgitta Agerberth

Birgitta Agerberth
Karolinska Institutet | KI · Department of Medical Biochemistry and Biophysics (MBB)

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190
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Publications

Publications (190)
Article
Full-text available
Aroylated phenylenediamines (APDs) are novel modulators of innate immunity with respect to enhancing the expression of antimicrobial peptides and maintaining epithelial barrier integrity. Here, we present a new study on induction of autophagy in human lung epithelial cells by the APD HO53. Interestingly, HO53 affected autophagy in a dose-dependent...
Article
K9CATH is the sole cathelicidin in canines (dogs) and exhibits broad antimicrobial activity against both Gram-positive and Gram-negative bacteria. K9CATH also modulates inflammatory responses and binds to LPS. These activities depend on the secondary structure and a net-positive charge of the peptide. Peptidylarginine deiminases (PAD) convert catio...
Article
Full-text available
In the gut, cathelicidin-related antimicrobial peptide (CRAMP) has been largely described for its anti-infective activities. With an increasing recognition of its immune regulatory effects in extra-intestinal diseases, the role of CRAMP in gluten-induced small intestinal enteropathy celiac disease remains unknown. This study aimed to investigate th...
Article
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Background Multidrug-resistant tuberculosis (MDR-TB) has low treatment success rates and new treatment strategies are needed. We explored if treatment with vitamin D (vitD) and phenylbutyrate (PBA) could improve conventional chemotherapy by enhancing immune-mediated eradication of Mycobacterium tuberculosis. Methods A clinically relevant model was...
Article
Full-text available
Background Diabetes mellitus type 2 (DM) may impede immune responses in tuberculosis (TB) and thus contribute to enhanced disease severity. In this study, we aimed to evaluate DM-mediated alterations in clinical, radiological and immunological outcomes in TB disease. Methods Newly diagnosed pulmonary TB patients with or without DM (TB n = 40; TB-D...
Article
Infections caused by multidrug resistant (MDR) Klebsiella pneumoniae are difficult to treat with conventional antibiotics. Thus, alternative strategies to control the growth of MDR Klebsiella are warranted. We hypothesized that activation of innate effector systems could sensitize MDR Klebsiella to conventional antibiotics. Thus, human primary macr...
Article
Full-text available
The innate immune system constitutes the first line of defense against invading pathogens, regulating the normal microbiota and contributes to homeostasis. Today we have obtained detailed knowledge on receptors, signaling pathways, and effector molecules of innate immunity. Our research constellation has focused on ways to induce the expression of...
Article
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Rationale: Biomarkers for the diagnosis of heart failure (HF) are clinically essential. Circulating antimicrobial peptides LL-37 has emerged as a novel biomarker in cardiovascular disease, however, its relevance as a biomarker for acute HF are undetermined. Methods: Acute HF patients were enrolled in this study and the serum levels of LL-37/CRAMP (...
Preprint
Full-text available
Background: Diabetes mellitus type 2 (DM) may impede immune responses in tuberculosis (TB) and thus contribute to enhanced disease severity. In this study, we aimed to evaluate DM-mediated alterations in clinical, radiological and immunological outcomes of TB disease. Methods: Newly diagnosed pulmonary TB patients with or without DM (TB n=40; TB-DM...
Preprint
Full-text available
Background: Diabetes mellitus type 2 (DM) may impede immune responses in tuberculosis (TB) and thus contribute to enhanced disease severity. In this study, we aimed to evaluate DM-mediated alterations in clinical, radiological and immunological outcomes of TB disease. Methods: Newly diagnosed pulmonary TB patients with or without DM (TB n=40; TB-DM...
Preprint
Full-text available
Background: Diabetes mellitus type 2 (DM) may impede immune responses in tuberculosis (TB) and thus contribute to enhanced disease severity. In this study, we aimed to evaluate DM-mediated alterations in clinical, radiological and immunological outcomes in TB disease. Methods: Newly diagnosed pulmonary TB patients with or without DM (TB n=40; TB-DM...
Preprint
Full-text available
Background: Diabetes mellitus type 2 (DM) may impede immune responses in tuberculosis (TB) and thus contribute to enhanced disease severity. In this study, we aimed to evaluate DM-mediated alterations in clinical, radiological and immunological outcomes in TB disease. Methods: Newly diagnosed pulmonary TB patients with or without DM (TB n=40; TB-DM...
Article
Full-text available
Arginine residues of the antimicrobial peptide LL-37 can be citrullinated by peptidyl arginine deiminases, which reduce the positive charge of the peptide. Notably, citrullinated LL-37 has not yet been detected in human samples. In addition, functional and biophysical properties of citrullinated LL-37 are not fully explored. The aim of this study w...
Article
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Background and purpose: Despite recent advances in understanding its pathophysiology, acute kidney injury (AKI) remains a major unmet medical need and novel therapeutic strategies are needed. Cathelicidin-related antimicrobial peptide (CRAMP) with immunomodulatory properties has an emerging role in various disease contexts. Here we aimed to invest...
Article
Full-text available
Tuberculosis (TB) is one of the leading causes of mortality and morbidity, particularly in developing countries, presenting a major threat to the public health. The currently recommended long term treatment regimen with multiple antibiotics is associated with poor patient compliance, which in turn, may contribute to the emergence of multi-drug resi...
Article
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In cutaneous Leishmaniasis the parasitic control in human host macrophages is still poorly understood. We found an increased expression of the human cathelicidin CAMP in skin lesions of Ethiopian patients with cutaneous leishmaniasis. Vitamin D driven, Cathelicidin-type antimicrobial peptides (CAMP) play an important role in the elimination of inva...
Article
Background: Antibiotic resistant Klebsiella pneumoniae (Kpn) constitute a great clinical challenge. One important resistance mechanism in Kpn are the metallo-β–lactamases (MBLs), which require zinc for their function. Thus, zinc chelation could be a strategy to resensitize Kpn to β-lactams. However, the potential role for endogenous zinc chelators...
Article
Scope: This study aims to examine the protective effects of specific low-methoxyl pectin (LMP) on the development of type 1 diabetes (T1D). Methods and results: Female non-obese diabetic (NOD) mice were weaned onto either control or 5% LMP supplemented diets for up to 22 weeks of age. T1D incidence, gut barrier function, and pancreatic-gut immun...
Article
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Intestinal homeostasis underpins the development of type 1 diabetes (T1D), and dietary manipulations to enhance intestinal homeostasis have been proposed to prevent T1D. The current study aimed to investigate the efficacy of supplementing a novel specific low-methoxyl pectin (LMP) dietary fiber in preventing T1D development. Female NOD mice were we...
Article
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Aroylated phenylenediamines (APDs) are novel inducers of innate immunity enhancing cathelicidin gene expression in human bronchial epithelial cell lines. Here we present two newly developed APDs and aimed at defining the response and signaling pathways for these compounds with reference to innate immunity and antimicrobial peptide (AMP) expression....
Article
Full-text available
Background: Cathelicidins are a major group of natural antimicrobial peptides which play essential roles in regulating host defense and immunity. In addition to the antimicrobial and immunomodulatory activities, recent studies have reported the involvement of cathelicidins in cardiovascular diseases by regulating inflammatory response and microvas...
Article
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Escherichia coli and Klebsiella pneumoniae are opportunistic pathogens that are commonly associated with infections at mucosal surfaces, such as the lung or the gut. The host response against these types of infections includes the release of epithelial-derived antimicrobial factors such as lipocalin-2 (LCN-2), a protein that specifically inhibits t...
Article
Ventilator associated pneumonia and sepsis are frequent complications in neonatal care. Bacterial colonization of medical devices and interfaces used for respiratory support may contribute by functioning as a bacterial reservoir seeding bacteria into airways. We have developed an antibacterial surface coating based on a cysteine ligand covalently c...
Preprint
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Tuberculosis (TB) is a global pandemic disease caused by Mycobacterium tuberculosis (Mtb) that is responsible for almost 9 million active pulmonary TB cases worldwide and about 1.5 million died from the disease in 2013 [1]. The prevalence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB is high and converge with the pandemics of...
Article
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Background: We have previously shown that 8 weeks' treatment with phenylbutyrate (PBA) (500mgx2/day) with or without vitamin D3 (vitD3) (5000 IU/day) as host-directed therapy (HDT) accelerated clinical recovery, sputum culture conversion and increased expression of cathelicidin LL-37 by immune cells in a randomized, placebo-controlled trial in adu...
Data
Effects of lactose on pancreatic B and T cells following acute pancreatitis induction. Female BALB/c mice were treated with caerulein together with or without lactose and 3 h later cells were recovered from the pancreas. Cells were directly stained for the expression of CD45, Ly6G, CD11b, CD19, and TCRβ. B and T cell numbers per pancreas were shown...
Data
Lactose treatment modulates the severity of experimental AP-associated lung injury. Lung myeloperoxidase activity (A) and histology (B) were determined. Vehicle: saline treatment. Caerulein: caerulein hyperstimulation treatment. Prophylactic: lactose administered 30 min before starting caerulein treatment. Therapeutic: lactose administered 1 h afte...
Article
Full-text available
Acute pancreatitis (AP) is one common clinical acute abdominal disease, for which specific pharmacological or nutritional therapies remain elusive. Lactose, a macronutrient and an inducer of host innate immune responses, possesses immune modulatory functions. The current study aimed to investigate potential modulatory effects of lactose and the int...
Article
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Objective Immunotherapy using vitamin D (vitD3) and phenylbutyrate (PBA), may support standard drug regimens used to treat infectious diseases. We investigated if vitD3+PBA enhanced clinical recovery from pulmonary tuberculosis (TB). Methods A randomized controlled trial was conducted in Addis Ababa, Ethiopia. Patients with smear‐positive or smear...
Article
The human host defense peptide, LL-37, is an important player in the first line of defense against invading microorganisms. LL-37 and its precursor, hCAP18, have been detected in unstimulated whole saliva but no reports showing hCAP18/LL-37 in isolated, parotid, and/or submandibular/sublingual saliva have been presented. Here, we measured the level...
Article
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Prostaglandin (PG)E2 is an arachidonic acid-derived lipid mediator that plays an important role in inflammation and immunity. In this study, we demonstrate that PGE2 suppresses basal and 1,25-dihydroxy vitamin D3 (VD3)-induced expression of hCAP18/LL-37 via E prostanoid (EP)2 and EP4 receptors. In humans, VD3 up-regulates vitamin D receptor (VDR) e...
Article
Antimicrobial peptides (AMPs) expressed by epithelial and immune cells have been described for immunomodulatory effects. However, the effects and potential mechanism of resident AMPs on acute kidney injury (AKI) remain unknown. Here, we found that serum cathelicidin-related antimicrobial peptide (CRAMP) levels were reduced in patients with AKI as c...
Chapter
One promising approach to meet the growing problem of antibiotic resistance is to modulate host defense mechanisms, i.e., host-directed therapy (HDT), in the fight against infections. Induction of endogenous antimicrobial peptides (AMPs) via small molecular compounds, such as 1,25-dihydroxyvitamin D3 or phenylbutyrate, could provide one such HDT-ba...
Article
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We have previously shown that oral treatment of an experimental model of shigellosis with sodium butyrate or phenylbutyrate improves clinical outcome and induces the expression of the antimicrobial peptide CAP-18 in the large intestinal epithelia. In a subsequent study, we have found that Entinostat, an aroylated phenylenediamine compound has simil...
Article
The type I interferon (IFN) system has recently been suggested to play important and essential roles in the pathogenesis of myositis. However, a clarification of how type I IFNs could function as triggering factor(s) in the pathogenesis of myositis has yet failed. Through activation of the type I IFN system, the host defense peptide LL-37 carries n...
Article
Full-text available
A new concept for treatment of infections is induction of our own antimicrobial peptides and the presented novel class of inducer, aroylated phenylenediamines (APDs), gives up to 20 to 30-fold induction of the human antimicrobial peptide LL-37, in vitro. In addition, oral administration of an APD in a rabbit model of Shigellosis resulted in recover...
Article
Full-text available
Bacterial resistance against classical antibiotics is a growing problem and the development of new antibiotics is limited. Thus, novel alternatives to antibiotics are warranted. Antimicrobial peptides (AMPs) are effector molecules of innate immunity that can be induced by several compounds, including vitamin D and phenyl-butyrate (PBA). Utilizing a...
Article
Background The human antimicrobial peptide LL-37, exhibits a variety of biological functions such as activation of plasmacytoid dendritic cells (pDC) to produce type I interferon and mediate tissue damage. In autoimmune diseases such as systemic lupus erythematosus, rheumatic arthritis, and psoriasis LL-37 released by neutrophils is overexpressed a...
Article
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Cathelicidins are pleiotropic antimicrobial peptides largely described for innate antimicrobial defenses and, more recently, immunomodulation. They are shown to modulate a variety of immune or nonimmune host cell responses. However, how cathelicidins are expressed by β cells and modulate β-cell functions under steady-state or proinflammatory condit...
Article
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Background: Development of new tuberculosis (TB) drugs and alternative treatment strategies are urgently required to control the global spread of TB. Previous results have shown that vitamin D3 (vitD3) and 4-phenyl butyrate (PBA) are potent inducers of the host defense peptide LL-37 that possess anti-mycobacterial effects. Objective: To examine...
Article
Glucocorticoids (GCs) have been extensively used as the mainstream treatment for chronic inflammatory disorders. The persistent use of steroids in the past decades and the association with secondary infections warrants for detailed investigation into their effects on the innate immune system and the therapeutic outcome. In this study, we analyse th...
Article
Full-text available
Antimicrobial peptides (AMPs) expressed by epithelial and immune cells are largely described for the defense against invading microorganisms. Recently, their immunomodulatory functions have been highlighted in various contexts. However how AMPs expressed by non-immune cells might influence autoimmune responses in peripheral tissues, such as the pan...
Article
Full-text available
LL-37 is a human antimicrobial peptide (AMP) of the cathelicidin family with multiple activities including a mediator of vitamin D-induced autophagy in human macrophages, resulting in intracellular killing of Mycobacterium tuberculosis (Mtb). In a previous trial in healthy volunteers, we have shown that LL-37 expression and subsequent Mtb-killing c...
Article
Full-text available
Apart from their role in the immune defence against pathogens evidence of a role of antimicrobial peptides (AMPs) in autoimmune diseases has accumulated in the past years. The aim of this project was to examine the functional impact of the human cathelicidin LL-37 and the mouse cathelicidin-related AMP (CRAMP) on the pathogenesis of lupus and arthr...
Article
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Narcolepsy is a chronic sleep disorder, likely with an autoimmune component. During 2009 and 2010, a link between A(H1N1)pdm09 Pandemrix vaccination and onset of narcolepsy was suggested in Scandinavia. In this study, we searched for autoantibodies related to narcolepsy using a neuroanatomical array: rat brain sections were processed for immunohist...
Article
Full-text available
Antibiotics exert several effects on host cells including regulation of immune components. Antimicrobial peptides (AMPs), e.g., cathelicidins and defensins display multiple functions in innate immunity. In colonic mucosa, cathelicidins are induced by butyrate, a bacterial fermentation product. Here, we investigated the effect of antibiotics on buty...
Article
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Unlabelled: At birth, the foetus makes the transition from the uterus to a world full of microbes. The newborn baby needs protection against potential invading pathogens and needs to establish a normal microbiota. Conclusion: Antimicrobial peptides and proteins are key effector molecules of innate immunity and are also important immunomodulators...
Article
Full-text available
In humans, LL-37 and eicosanoids are important mediators of inflammation and immune responses. Here we report that LL-37 promotes leukotriene B4 (LTB4) and thromboxane A2 (TXA2) generation by human monocyte-derived macrophages (HMDMs). LL-37 evokes calcium mobilization apparently via the P2X7 receptor (P2X7R), activation of ERK1/2 and p38 MAPKs, as...