IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection

Sci Adv. 2020 Apr 1;6(14):eaay3245. doi: 10.1126/sciadv.aay3245. eCollection 2020 Apr.

Abstract

In the skin, antiviral proteins and other immune molecules serve as the first line of innate antiviral defense. Here, we identify and characterize the induction of cutaneous innate antiviral proteins in response to IL-27 and its functional role during cutaneous defense against Zika virus infection. Transcriptional and phenotypic profiling of epidermal keratinocytes treated with IL-27 demonstrated activation of antiviral proteins OAS1, OAS2, OASL, and MX1 in the skin of both mice and humans. IL-27-mediated antiviral protein induction was found to occur in a STAT1- and IRF3-dependent but STAT2-independent manner. Moreover, using IL27ra mice, we demonstrate a significant role for IL-27 in inhibiting Zika virus morbidity and mortality following cutaneous, but not intravenous, inoculation. Together, our results demonstrate a critical and previously unrecognized role for IL-27 in cutaneous innate antiviral immunity against Zika virus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Cell Line
  • Cells, Cultured
  • Cytokines / metabolism
  • Disease Resistance* / immunology
  • Gene Expression
  • Host-Pathogen Interactions* / immunology
  • Humans
  • Immunity, Innate*
  • Interleukins / metabolism*
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • Keratinocytes / virology
  • STAT1 Transcription Factor / metabolism
  • Signal Transduction*
  • Skin / immunology
  • Skin / metabolism
  • Skin / virology
  • Zika Virus / immunology*
  • Zika Virus Infection / etiology*
  • Zika Virus Infection / metabolism*

Substances

  • Biomarkers
  • Cytokines
  • Interleukins
  • MYDGF protein, human
  • STAT1 Transcription Factor
  • STAT1 protein, human