Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation
Year: 2014
Type: article
Abstract: Chitin is an essential structural polysaccharide of fungal pathogens and parasites, but its role in human immune responses remains largely unknown. It is the second most abundant polysaccharide in nature after cellulose and its derivatives today are widely used for medical and industrial purposes. We analysed the immunological properties of purified chitin particles derived from the opportunistic human fungal pathogen Candida albicans, which led to the selective secretion of the anti-inflammatory cytokine IL-10. We identified NOD2, TLR9 and the mannose receptor as essential fungal chitin-recognition receptors for the induction of this response. Chitin reduced LPS-induced inflammation in vivo and may therefore contribute to the resolution of the immune response once the pathogen has been defeated. Fungal chitin also induced eosinophilia in vivo, underpinning its ability to induce asthma. Polymorphisms in the identified chitin receptors, NOD2 and TLR9, predispose individuals to inflammatory conditions and dysregulated expression of chitinases and chitinase-like binding proteins, whose activity is essential to generate IL-10-inducing fungal chitin particles in vitro, have also been linked to inflammatory conditions and asthma. Chitin recognition is therefore critical for immune homeostasis and is likely to have a significant role in infectious and allergic disease.
Source: PLoS Pathogens
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,286
Funders: Wellcome Trust, American Lebanese Syrian Associated Charities, European Commission, University of Bath, University of Aberdeen, Deutsche Forschungsgemeinschaft, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Medical Research Council, Biotechnology and Biological Sciences Research Council, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Dental and Craniofacial Research
Awards: G1147502531, Role of IL-1alpha signaling in inflammatory diseases and host defense, The role and modulation of Dectin-1 function in innate and adaptive immunity., Wellcome Strategic Award for Medical Mycology and Fungal Immunology, G2851941416, The fungal "septasome": dividing and conquering cells of fungal pathogens, Regulation of the biosynthesis of the cell wall skeleton of Candida albicans., G3127346458, G3789341260, G4014380164, G4017778674, Wellcome Strategic Award for Medical Mycology and Fungal Immunology, Making and breaking the cell walls of fungal pathogens., G5026717116, G5161360796, Combinatorial responses of fungal pathogens to their human hosts: an Integrative Systems Biology approach, G5372223083, G5702163051, G62698875, Pathogenomics and Systems Biology of Fungal Infections – An Integrative Approach, Candida albicans cell surface: regulation of the host-fungus interaction., G6798282112, G7087521619, Fungi in the setting of inflammation, allergy and autoimmune diseases:Translating basic science into clinical practices, Inflammatory Caspases in Innate Immunity and Inflammation, G8167955467, Imaging the Morphogenesis, Cell Division and Growth of Microorganisms., C-type lectins in antifungal immunity, G9000023059, Inflammatory Caspases in Innate Immunity and Inflammation
OpenAlex ID: W2065616962