Endosomal TLR3 co-receptor CLEC18A enhances host immune response to viral infection.
Commun Biol
; 4(1): 229, 2021 02 18.
Article
em En
| MEDLINE
| ID: mdl-33603190
ABSTRACT
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 âR339) 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 (IC) specifically. Compared to TLR3 alone, binding affinity to poly (IC) 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 (IC) 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 (IC) and IAV infection between human and mouse.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endossomos
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Infecções por Orthomyxoviridae
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Lectinas Tipo C
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Receptor 3 Toll-Like
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Virus da Influenza A Subtipo H5N1
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Commun Biol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Taiwan