Journal Article

DKFZ-2018-01716

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The fungal ligand chitin directly binds TLR2 and triggers inflammation dependent on oligomer size.

Fuchs, K. ; Cardona Gloria, Y. ; Wolz, O.-O. ; Herster, F. ; Sharma, L. ; Dillen, C. A. ; Täumer, C. ; Dickhöfer, S. ; Bittner, Z. ; Dang, T.-M. ; Singh, A. ; Haischer, D. ; Schlöffel, M. A. ; Koymans, K. J. ; Sanmuganantham, T. ; Krach, M. ; Roger, T. ; Le Roy, D. ; Schilling, N. A. ; Frauhammer, F.DKFZ* ; Miller, L. S. ; Nürnberger, T. ; LeibundGut-Landmann, S. ; Gust, A. A. ; Macek, B. ; Frank, M. ; Gouttefangeas, C. ; Dela Cruz, C. S. ; Hartl, D. ; Weber, A. N.

2018
Wiley Hoboken, NJ [u.a.]

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Please use a persistent id in citations: doi:10.15252/embr.201846065

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.

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Contributing Institute(s):

1. Angewandte Bioinformatik (G200)

Research Program(s):

1. 317 - Translational cancer research (POF3-317) (POF3-317)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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