Endosomal TLR3 co-receptor CLEC18A enhances host immune response to viral infection

Ya Lang Huang, Ming Ting Huang, Pei Shan Sung, Teh Ying Chou, Ruey Bing Yang, An Suei Yang, Chung Ming Yu, Yu Wen Hsu, Wei Chiao Chang, Shie Liang Hsieh

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2 引文 斯高帕斯(Scopus)

摘要

Human C-type lectin member 18A (CLEC18A) is ubiquitously expressed in human, and highest expression levels are found in human myeloid cells and liver. In contrast, mouse CLEC18A (mCLEC18A) is only expressed in brain, kidney and heart. However, the biological functions of CLEC18A are still unclear. We have shown that a single amino acid change (S339 →R339) in CTLD domain has profound effect in their binding to polysaccharides and house dust mite allergens. In this study, we further demonstrate that CLEC18A and its mutant CLEC18A(S339R) associate with TLR3 in endosome and bind poly (I:C) specifically. Compared to TLR3 alone, binding affinity to poly (I:C) is further increased in TLR3-CLEC18A and TLR3-CLEC18A(S339R) complexes. Moreover, CLEC18A and CLEC18A(S339R) enhance the production of type I and type III interferons (IFNs), but not proinflammatory cytokines, in response to poly (I:C) or H5N1 influenza A virus (IAV) infection. Compared to wild type (WT) mice, ROSA-CLEC18A and ROSA-CLEC18A(S339R) mice generate higher amounts of interferons and are more resistant to H5N1 IAV infection. Thus, CLEC18A is a TLR3 co-receptor, and may contribute to the differential immune responses to poly (I:C) and IAV infection between human and mouse.
原文英語
文章編號229
期刊Communications Biology
4
發行號1
DOIs
出版狀態已發佈 - 十二月 2021

ASJC Scopus subject areas

  • 生物化學、遺傳與分子生物學 (全部)
  • 農業與生物科學 (全部)
  • 醫藥(雜項)
  • 醫藥 (全部)

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