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

Research output: Contribution to journalArticle

120 Citations (Scopus)
3 Downloads (Pure)

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

Fingerprint

Chitin
Interleukin-10
Inflammation
Chitinases
Cell Wall
Immune System
Toll-Like Receptor 9
Mycoses
Cellulose
Crohn Disease
Polysaccharides
Carrier Proteins
Fungi
Anti-Inflammatory Agents
Asthma
Cytokines
Mutation
Health
Enzymes
Infection

Cite this

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.

In: PLoS Pathogens, Vol. 10, No. 4, e1004050, 10.04.2014.

Research output: Contribution to journalArticle

Wagener, J, Malireddi, RKS, Lenardon, MD, Köberle, M, Vautier, S, Maccallum, DM, Biedermann, T, Schaller, M, Netea, MG, Kanneganti, T-D, Brown, GD, Brown, AJP & Gow, NAR 2014, 'Fungal chitin dampens inflammation through IL-10 induction mediated by NOD2 and TLR9 activation', PLoS Pathogens, vol. 10, no. 4, e1004050. https://doi.org/10.1371/journal.ppat.1004050
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. In: PLoS Pathogens. 2014 ; Vol. 10, No. 4.
@article{576791a8d8dc4bc68116445b807e79e8,
title = "Fungal chitin dampens inflammation through IL-10 induction mediated by NOD2 and TLR9 activation",
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.",
author = "Jeanette Wagener and Malireddi, {R K Subbarao} and Lenardon, {Megan D} and Martin K{\"o}berle and Simon Vautier and Maccallum, {Donna M} and Tilo Biedermann and Martin Schaller and Netea, {Mihai G} and Thirumala-Devi Kanneganti and Brown, {Gordon D} and Brown, {Alistair J P} and Gow, {Neil A R}",
year = "2014",
month = "4",
day = "10",
doi = "10.1371/journal.ppat.1004050",
language = "English",
volume = "10",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "4",

}

TY - JOUR

T1 - Fungal chitin dampens inflammation through IL-10 induction mediated by NOD2 and TLR9 activation

AU - Wagener, Jeanette

AU - Malireddi, R K Subbarao

AU - Lenardon, Megan D

AU - Köberle, Martin

AU - Vautier, Simon

AU - Maccallum, Donna M

AU - Biedermann, Tilo

AU - Schaller, Martin

AU - Netea, Mihai G

AU - Kanneganti, Thirumala-Devi

AU - Brown, Gordon D

AU - Brown, Alistair J P

AU - Gow, Neil A R

PY - 2014/4/10

Y1 - 2014/4/10

N2 - 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.

AB - 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.

U2 - 10.1371/journal.ppat.1004050

DO - 10.1371/journal.ppat.1004050

M3 - Article

C2 - 24722226

VL - 10

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 4

M1 - e1004050

ER -