Fungal chitin dampens inflammation through IL-10 induction mediated by NOD2 and TLR9 activation

Jeanette Wagener, R K Subbarao Malireddi, Megan D Lenardon, Martin Köberle, Simon Vautier, Donna M Maccallum, Tilo Biedermann, Martin Schaller, Mihai G Netea, Thirumala-Devi Kanneganti, Gordon D Brown, Alistair J P Brown, Neil A R Gow

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Abstract

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.
Original languageEnglish
Article numbere1004050
Number of pages15
JournalPLoS Pathogens
Volume10
Issue number4
DOIs
Publication statusPublished - 10 Apr 2014

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