CLEC5A: A Promiscuous Pattern Recognition Receptor to Microbes and Beyond

Advances in Experimental Medicine and Biology
Pei-Shan SungShie-Liang Hsieh

Abstract

CLEC5A is a spleen tyrosine kinase (Syk)-coupled C-type lectin that is highly expressed by monocytes, macrophages, neutrophils, and dendritic cells and interacts with virions directly, via terminal fucose and mannose moieties of viral glycans. CLEC5A also binds to N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) disaccharides of bacterial cell walls. Compared to other C-type lectins (DC-SIGN and DC-SIGNR) and TLRs, CLEC5A binds its ligands with relatively low affinities. However, CLEC5A forms a multivalent hetero-complex with DC-SIGN and other C-type lectins upon engagement with ligands, and thereby mediates microbe-induced inflammatory responses via activation of Syk. For example, in vivo studies in mouse models have demonstrated that CLEC5A is responsible for flaviviruses-induced hemorrhagic shock and neuroinflammation, and a CLEC5A polymorphism in humans is associated with disease severity following infection with dengue virus. In addition, CLEC5A is co-activated with TLR2 by Listeria and Staphylococcus. Furthermore, CLEC5A-postive myeloid cells are responsible for Concanavilin A-induced aseptic inflammatory reactions. Thus, CLEC5A is a promiscuous pattern recognition receptor in myeloid cells and is a potentia...Continue Reading

Citations

Feb 23, 2020·The Journal of Pathology·Siamon GordonSubhankar Mukhopadhyay
Jun 13, 2021·Journal of Biomedical Science·Pei-Shan Sung, Shie-Liang Hsieh
Sep 9, 2021·Chembiochem : a European Journal of Chemical Biology·Hans-Joachim GabiusAntonio Romero

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Methods Mentioned

BETA
X-ray
glycosylation
genotyping

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