Title

TLR8 Couples SOCS-1 and Restrains TLR7-Mediated Antiviral Immunity, Exacerbating West Nile Virus Infection in Mice

Document Type

Article

Publication Date

12-1-2016

Department

Biological Sciences

Abstract

West Nile virus (WNV) is a neurotropic ssRNA flavivirus that can cause encephalitis, meningitis, and death in humans and mice. Human TLR7 and TLR8 and mouse TLR7 recognize viral ssRNA motifs and induce antiviral immunity. However, the role of mouse TLR8 in antiviral immunity is poorly understood. In this article, we report that TLR8-deficient (Tlr8−/−) mice were resistant to WNV infection compared with wild-type controls. Efficient WNV clearance and moderate susceptibility to WNV-mediated neuronal death in Tlr8−/− mice were attributed to overexpression of Tlr7and IFN-stimulated gene-56 expression, whereas reduced expression of the proapoptotic gene coding Bcl2-associated X protein was observed. Interestingly, suppressor of cytokine signaling (SOCS)-1 directly associated with TLR8, but not with TLR7, indicating a novel role for TLR8 regulation of SOCS-1 function, whereas selective small interfering RNA knockdown of Socs-1 resulted in induced IFN-stimulated gene-56 and Tlr7 expression following WNV infection. Collectively, we report that TLR8 coupling with SOCS-1 inhibits TLR7-mediated antiviral immunity during WNV infection in mice.

Publication Title

The Journal of Immunology

Volume

197

Issue

11

First Page

4425

Last Page

4435

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