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

doi:10.1371/journal.ppat.1004050

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^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Article number	e1004050
Number of pages	15
Journal	PLoS Pathogens
Volume	10
Issue number	4
DOIs	https://doi.org/10.1371/journal.ppat.1004050
Publication status	Published - 10 Apr 2014

Bibliographical note

Funding:
JW and NARG thank the Wellcome Trust (080088, 086827, 075470), The Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377) and the European Union ALLFUN (FP7/2007 2013, HEALTH-2010-260338) for funding. MGN was supported by a Vici grant of the Netherlands Organisation for Scientific Research. AJPB and DMM were funded by STRIFE, ERC-2009-AdG-249793 and AJPB additionally by FINSysB, PITN-GA-2008-214004 and the BBSRC [BB/F00513X/1]. MDL was supported by the MRC (MR/J008230/1). GDB and SV were funded by the Wellcome Trust (086558) and TB and MK were funded by the Deutsche Forschungsgemeinschaft (Bi 696/3-1; Bi 696/5-2; Bi 696/10-1). MS was supported by the Deutsche Forschungsgemeinschaft (Sch 897/1-3) and the National Institute of Dental and Craniofacial Research (R01 DE017514-01). TDK and RKSM were funded by the National Institute of Health (AR056296, AI101935) and the American Lebanese Syrian Associated Charities (ALSAC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Keywords

Chitin
Secretion
Candida albicans
Cytokines
Macrophages
Cell walls
Inflammation
Fungal phatogens

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.ppat.1004050Licence: CC BY

Fungal chitin
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Final published version, 1.87 MBLicence: CC BY

Donna MacCallum
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Wagener, J., Malireddi, R. K. S., Lenardon, M. D., Köberle, M., Vautier, S., MacCallum, D. M., Biedermann, T., Schaller, M., Netea, M. G., Kanneganti, T.-D., Brown, G. D., Brown, A. J. P., & Gow, N. A. R. (2014). Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation. PLoS Pathogens, 10(4), Article e1004050. https://doi.org/10.1371/journal.ppat.1004050

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title = "Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation",

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.",

keywords = "Chitin, Secretion, Candida albicans, Cytokines, Macrophages, Cell walls, Inflammation, Fungal phatogens",

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}",

note = "Funding: JW and NARG thank the Wellcome Trust (080088, 086827, 075470), The Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377) and the European Union ALLFUN (FP7/2007 2013, HEALTH-2010-260338) for funding. MGN was supported by a Vici grant of the Netherlands Organisation for Scientific Research. AJPB and DMM were funded by STRIFE, ERC-2009-AdG-249793 and AJPB additionally by FINSysB, PITN-GA-2008-214004 and the BBSRC [BB/F00513X/1]. MDL was supported by the MRC (MR/J008230/1). GDB and SV were funded by the Wellcome Trust (086558) and TB and MK were funded by the Deutsche Forschungsgemeinschaft (Bi 696/3-1; Bi 696/5-2; Bi 696/10-1). MS was supported by the Deutsche Forschungsgemeinschaft (Sch 897/1-3) and the National Institute of Dental and Craniofacial Research (R01 DE017514-01). TDK and RKSM were funded by the National Institute of Health (AR056296, AI101935) and the American Lebanese Syrian Associated Charities (ALSAC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.",

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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

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N2 - 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.

AB - 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.

KW - Chitin

KW - Secretion

KW - Candida albicans

KW - Cytokines

KW - Macrophages

KW - Cell walls

KW - Inflammation

KW - Fungal phatogens

U2 - 10.1371/journal.ppat.1004050

DO - 10.1371/journal.ppat.1004050

M3 - Article

C2 - 24722226

SN - 1553-7366

VL - 10

JO - PLoS Pathogens

JF - PLoS Pathogens

IS - 4

M1 - e1004050

ER -

Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation

Abstract

Bibliographical note

Keywords

UN SDGs

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Donna MacCallum

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