Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation
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. W...
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2014
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pubmed-39830642014-04-15 Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation 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. Research Article 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. Public Library of Science 2014-04-10 /pmc/articles/PMC3983064/ /pubmed/24722226 http://dx.doi.org/10.1371/journal.ppat.1004050 Text en © 2014 Wagener et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
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Open Access Journal |
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Foreign Institution |
institution |
US National Center for Biotechnology Information |
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NCBI PubMed |
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Online Access |
language |
English |
format |
Online |
author |
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. |
spellingShingle |
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. Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation |
author_facet |
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. |
author_sort |
Wagener, Jeanette |
title |
Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation |
title_short |
Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation |
title_full |
Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation |
title_fullStr |
Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation |
title_full_unstemmed |
Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation |
title_sort |
fungal chitin dampens inflammation through il-10 induction mediated by nod2 and tlr9 activation |
description |
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. |
publisher |
Public Library of Science |
publishDate |
2014 |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983064/ |
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1612076838257950720 |