TY - JOUR
T1 - Endosomal TLR3 co-receptor CLEC18A enhances host immune response to viral infection
AU - Huang, Ya Lang
AU - Huang, Ming Ting
AU - Sung, Pei Shan
AU - Chou, Teh Ying
AU - Yang, Ruey Bing
AU - Yang, An Suei
AU - Yu, Chung Ming
AU - Hsu, Yu Wen
AU - Chang, Wei Chiao
AU - Hsieh, Shie Liang
N1 - Funding Information:
This work was supported by the Academia Sinica Investigator Award (AS-IA-109-L02), Summit Research Projects and grant 109-2101-01-19-20 (Academia Sinica), Ministry of Science and Technology (MOST 107-2321-B-001-015), and VGH, TSGH, and AS Joint Research Program (VTA109-A-3-1). We thank the Taiwan Mouse Clinic (TMC) and Transgenic Mouse Model Core Facility (TMMC), which are funded by the National Research Program for Genomic Medicine (NRPGM) at the National Science Council of Taiwan, for technical support in histopathology experiments.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s42003-021-01745-7
DO - 10.1038/s42003-021-01745-7
M3 - Article
C2 - 33603190
AN - SCOPUS:85101223736
SN - 2399-3642
VL - 4
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 229
ER -