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The fungal ligand chitin directly binds <scp>TLR</scp> 2 and triggers inflammation dependent on oligomer size

Authors :
Kirsten J. Koymans
Alexander N.R. Weber
Cécile Gouttefangeas
Carly A. Dillen
Sabine Dickhöfer
Christoph Taumer
Zsofia Bittner
Daniel J. Haischer
Boris Macek
Thorsten Nürnberger
Andrea A. Gust
Milena Krach
Martin Frank
Anurag Singh
Nadine A. Schilling
Didier Le Roy
Felix Frauhammer
Tharmila Sanmuganantham
Olaf Oliver Wolz
Salomé LeibundGut-Landmann
Truong Minh Dang
Lloyd S. Miller
Katharina Fuchs
Thierry Roger
Yamel Cardona Gloria
Charles S. Dela Cruz
Maria A. Schlöffel
Franziska Herster
Lokesh Sharma
Dominik Hartl
Source :
EMBO reports. 19
Publication Year :
2018
Publisher :
EMBO, 2018.

Abstract

Chitin is the second most abundant polysaccharide in nature and linked to fungal infection and asthma. However, bona fide immune receptors directly binding chitin and signaling immune activation and inflammation have not been clearly identified because polymeric crude chitin with unknown purity and molecular composition has been used. By using defined chitin (N‐acetyl‐glucosamine) oligomers, we here identify six‐subunit‐long chitin chains as the smallest immunologically active motif and the innate immune receptor Toll‐like receptor (TLR2) as a primary fungal chitin sensor on human and murine immune cells. Chitin oligomers directly bind TLR2 with nanomolar affinity, and this fungal TLR2 ligand shows overlapping and distinct signaling outcomes compared to known mycobacterial TLR2 ligands. Unexpectedly, chitin oligomers composed of five or less subunits are inactive, hinting to a size‐dependent system of immuno‐modulation that appears conserved in plants and humans. Since blocking of the chitin‐TLR2 interaction effectively prevents chitin‐mediated inflammation in vitro and in vivo, our study highlights the chitin‐TLR2 interaction as a potential target for developing novel therapies in chitin‐related pathologies and fungal disease.

Details

ISSN :
14693178 and 1469221X
Volume :
19
Database :
OpenAIRE
Journal :
EMBO reports
Accession number :
edsair.doi.dedup.....a3c58fdaf8d0a8ed6819c4cc1cb634df
Full Text :
https://doi.org/10.15252/embr.201846065