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The fungal ligand chitin directly binds TLR 2 and triggers inflammation dependent on oligomer size
Author(s) -
Fuchs Katharina,
Cardona Gloria Yamel,
Wolz OlafOliver,
Herster Franziska,
Sharma Lokesh,
Dillen Carly A,
Täumer Christoph,
Dickhöfer Sabine,
Bittner Zsofia,
Dang TruongMinh,
Singh Anurag,
Haischer Daniel,
Schlöffel Maria A,
Koymans Kirsten J,
Sanmuganantham Tharmila,
Krach Milena,
Roger Thierry,
Le Roy Didier,
Schilling Nadine A,
Frauhammer Felix,
Miller Lloyd S,
Nürnberger Thorsten,
LeibundGutLandmann Salomé,
Gust Andrea A,
Macek Boris,
Frank Martin,
Gouttefangeas Cécile,
Dela Cruz Charles S,
Hartl Dominik,
Weber Alexander NR
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201846065
Subject(s) - chitin , tlr2 , innate immune system , immune system , biology , receptor , pattern recognition receptor , biochemistry , toll like receptor , chemistry , microbiology and biotechnology , immunology , chitosan
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 ( TLR 2) as a primary fungal chitin sensor on human and murine immune cells. Chitin oligomers directly bind TLR 2 with nanomolar affinity, and this fungal TLR 2 ligand shows overlapping and distinct signaling outcomes compared to known mycobacterial TLR 2 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‐ TLR 2 interaction effectively prevents chitin‐mediated inflammation in vitro and in vivo , our study highlights the chitin‐ TLR 2 interaction as a potential target for developing novel therapies in chitin‐related pathologies and fungal disease.