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The fungal ligand chitin directly binds <scp>TLR</scp> 2 and triggers inflammation dependent on oligomer size
- 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.
- Subjects :
- 0301 basic medicine
THP-1 Cells
Chitin
macromolecular substances
Ligands
Polysaccharide
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Immune system
Cell Wall
Genetics
Animals
Humans
Immunologic Factors
Lymphocytes
Receptor
Molecular Biology
Inflammation
Mice, Knockout
chemistry.chemical_classification
Toll-like receptor
Innate immune system
Chitinases
Scientific Reports
fungi
Fungi
Zymosan
Toll-Like Receptor 1
Toll-Like Receptor 2
In vitro
Mice, Inbred C57BL
carbohydrates (lipids)
TLR2
030104 developmental biology
chemistry
Female
Hydrophobic and Hydrophilic Interactions
030215 immunology
Subjects
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