Activation of STAT6 by STING Is Critical for Antiviral Innate Immunity

Cell. 2011 Oct 14;147(2):436-46. doi: 10.1016/j.cell.2011.09.022.

Abstract

STAT6 plays a prominent role in adaptive immunity by transducing signals from extracellular cytokines. We now show that STAT6 is required for innate immune signaling in response to virus infection. Viruses or cytoplasmic nucleic acids trigger STING (also named MITA/ERIS) to recruit STAT6 to the endoplasmic reticulum, leading to STAT6 phosphorylation on Ser(407) by TBK1 and Tyr(641), independent of JAKs. Phosphorylated STAT6 then dimerizes and translocates to the nucleus to induce specific target genes responsible for immune cell homing. Virus-induced STAT6 activation is detected in all cell-types tested, in contrast to the cell-type specific role of STAT6 in cytokine signaling, and Stat6(-/-) mice are susceptible to virus infection. Thus, STAT6 mediates immune signaling in response to both cytokines at the plasma membrane, and virus infection at the endoplasmic reticulum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Base Sequence
  • Immunity, Innate*
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA Virus Infections / immunology*
  • RNA Viruses*
  • STAT6 Transcription Factor / genetics
  • STAT6 Transcription Factor / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • IPS-1 protein, mouse
  • MPYS protein, mouse
  • Membrane Proteins
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Tbk1 protein, mouse
  • Protein-Serine-Threonine Kinases