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. 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.
Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
Jeanette
J
Wagener
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
R K Subbarao
RK
Malireddi
Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
Megan D
MD
Lenardon
Department of Dermatology, Eberhard Karls University Tübingen, Tübingen, Germany.
Martin
M
Köberle
Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
Simon
S
Vautier
Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
Donna M
DM
MacCallum
Department of Dermatology, Eberhard Karls University Tübingen, Tübingen, Germany.
Tilo
T
Biedermann
Department of Dermatology, Eberhard Karls University Tübingen, Tübingen, Germany.
Martin
M
Schaller
Department of Internal Medicine and Nijmegen Institute for Infection, Inflammation & Immunity (N4i), Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Mihai G
MG
Netea
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Thirumala-Devi
TD
Kanneganti
Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
Gordon D
GD
Brown
Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
Alistair J P
AJ
Brown
Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
Neil A R
NA
Gow
D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D002176:Candida albicans / Q000737:chemistry* / Q000276:immunology; D002686:Chitin / Q000737:chemistry / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology*
C508609:IL10 protein, human; C556062:IL10 protein, mouse; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; C495371:TLR9 protein, human; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D016753:Interleukin-10; D002686:Chitin