Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation
| Autor: | Wagener, Jeanette, Malireddi, R. K. Subbarao, Lenardon, Megan D., Köberle, Martin, Vautier, Simon, MacCallum, Donna M., Biedermann, Tilo, Schaller, Martin, Netea, Mihai G., Kanneganti, Thirumala-Devi, Brown, Gordon D., Brown, Alistair J. P., Gow, Neil A. R. |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Fungal Structure QH301-705.5 Immunology Glycobiology Nod2 Signaling Adaptor Protein Chitin Mycology Pathogenesis macromolecular substances Pathology and Laboratory Medicine Biochemistry Immune Suppression Microbiology Immunomodulation Immune Activation Mice Polysaccharides Candida albicans Immune Tolerance Medicine and Health Sciences Animals Humans Biology (General) Immune Response Immunity to Infections Inflammation Innate Immune System Immunity Organisms Fungi Biology and Life Sciences Immunoregulation Molecular Development RC581-607 Yeast Asthma Interleukin-10 carbohydrates (lipids) Immune System Toll-Like Receptor 9 Host-Pathogen Interactions Cytokines Clinical Immunology Female Immunologic diseases. Allergy Research Article Developmental Biology |
| Zdroj: | PLoS Pathogens; Vol 10 PLoS Pathogens PLoS Pathogens, Vol 10, Iss 4, p e1004050 (2014) |
| ISSN: | 1553-7374 |
| DOI: | 10.1371/journal.ppat.1004050 |
| Popis: | 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. Authors Summary Chitin is the second most abundant polysaccharide in nature after cellulose and an essential component of the cell wall of all fungal pathogens. The discovery of human chitinases and chitinase-like binding proteins indicates that fungal chitin is recognised by cells of the human immune system, shaping the immune response towards the invading pathogen. We show that three immune cell receptors– the mannose receptor, NOD2 and TLR9 recognise chitin and act together to mediate an anti-inflammatory response via secretion of the cytokine IL-10. This mechanism may prevent inflammation-based damage during fungal infection and restore immune balance after an infection has been cleared. By increasing the chitin content in the cell wall pathogenic fungi may influence the immune system in their favour, by down-regulating protective inflammatory immune responses. Furthermore, gene mutations and dysregulated enzyme activity in the described chitin recognition pathway are implicated in inflammatory conditions such as Crohn's Disease and asthma, highlighting the importance of the discovered mechanism in human health. |
| Databáze: | OpenAIRE |
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