IL-36 promotes anti-viral immunity by boosting sensitivity to IFN-α/β in IRF1 dependent and independent manners.

ABSTRACT: The functions of the IL-36 cytokines remain poorly understood. We report a previously unrecognized mechanism whereby IL-36 promotes innate antiviral immunity in mouse and human models of herpes simplex virus-1 (HSV-1) infections. HSV-1 actively suppresses production of type I interferon (IFN); our data reveal that IL-36 overcomes this immune evasion strategy by increasing cellular sensitivity to IFN. IL-36β deficient mice display impaired IFN responses and poorly restrict viral replication in skin keratinocytes. In mouse and human keratinocytes IL-36 elicits an antiviral state driven by STAT1 and STAT2 via enhanced expression of IFNAR1 and IFNAR2 subunits of the type I IFN receptor. The degree of IFN regulatory factor 1 (IRF1) involvement is species dependent, with IRF1 playing a more prom

SUBMITTER: Wang P 

PROVIDER: S-EPMC6795910 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature