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CLEC5A: A Promiscuous Pattern Recognition Receptor to Microbes and Beyond.

Pei-Shan Sung1, Wei-Chiao Chang2, Shie-Liang Hsieh3,4

  • 1Genomics Research Center, Academia Sinica, Taipei, Taiwan.

Advances in Experimental Medicine and Biology
|March 11, 2020
PubMed
Summary

The C-type lectin CLEC5A, expressed by myeloid cells, recognizes various microbial glycans. It mediates inflammatory responses and is a potential therapeutic target for septic and aseptic conditions.

Keywords:
CLEC5ADAP12ITAMMDL-1Syk

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Area of Science:

  • Immunology
  • Molecular Biology

Background:

  • CLEC5A is a C-type lectin expressed by myeloid cells, including monocytes, macrophages, neutrophils, and dendritic cells.
  • It functions as a spleen tyrosine kinase (Syk)-coupled receptor.
  • CLEC5A interacts with viral and bacterial glycans, such as terminal fucose, mannose, N-acetylglucosamine (GlcNAc), and N-acetylmuramic acid (MurNAc).

Purpose of the Study:

  • To investigate the role of CLEC5A in mediating inflammatory responses.
  • To explore CLEC5A as a potential therapeutic target for inflammatory diseases.

Main Methods:

  • The study involved analyzing CLEC5A's ligand-binding properties.
  • In vivo studies using mouse models were conducted to assess CLEC5A's function in disease.
  • Human genetic data was analyzed for CLEC5A polymorphism association with disease severity.

Main Results:

  • CLEC5A binds microbial glycans with relatively low affinity but forms multivalent complexes with other C-type lectins, activating Syk signaling.
  • In mouse models, CLEC5A mediates flavivirus-induced hemorrhagic shock and neuroinflammation.
  • A CLEC5A polymorphism is linked to dengue virus infection severity in humans.
  • CLEC5A is co-activated with TLR2 by Listeria and Staphylococcus, and mediates Concanavilin A-induced inflammation.

Conclusions:

  • CLEC5A acts as a promiscuous pattern recognition receptor in myeloid cells.
  • It plays a significant role in both septic and aseptic inflammatory reactions.
  • CLEC5A represents a potential therapeutic target for modulating inflammatory responses.