Interferon-Independent Activities of Mammalian STING Mediate Antiviral Response and Tumor Immune Evasion

Jianjun Wu, Nicole Dobbs, Kun Yang, Nan Yan

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Type I interferon (IFN) response is commonly recognized as the main signaling activity of STING. Here, we generate the Sting1S365A/S365A mutant mouse that precisely ablates IFN-dependent activities while preserving IFN-independent activities of STING. StingS365A/S365A mice protect against HSV-1 infection, despite lacking the STING-mediated IFN response. This challenges the prevailing view and suggests that STING controls HSV-1 infection through IFN-independent activities. Transcriptomic analysis reveals widespread IFN-independent activities of STING in macrophages and T cells, and STING activities in T cells are predominantly IFN independent. In mouse tumor models, T cells in the tumor experience substantial cell death that is in part mediated by IFN-independent activities of STING. We found that the tumor induces STING-mediated cell death in T cells to evade immune control. Our data demonstrate that mammalian STING possesses widespread IFN-independent activities that are important for restricting HSV-1 infection, tumor immune evasion and likely also adaptive immunity.

Original languageEnglish (US)
Pages (from-to)115-126.e5
JournalImmunity
Volume53
Issue number1
DOIs
StatePublished - Jul 14 2020

Keywords

  • HSV-1
  • IFN
  • STING
  • T cells
  • antiviral response
  • cancer immunology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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