STING Requires the Adaptor TRIF to Trigger Innate Immune Responses to Microbial Infection

Xin Wang, Tanmay Majumdar, Patricia Kessler, Evgeny Ozhegov, Ying Zhang, Saurabh Chattopadhyay, Sailen Barik, Ganes C. Sen

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

The intracellular microbial nucleic acid sensors, TLR3 and STING, recognize pathogen molecules and signal to activate the interferon pathway. The TIR-domain containing protein TRIF is the sole adaptor of TLR3. Here, we report an essential role for TRIF in STING signaling: various activators of STING could not induce genes in the absence of TRIF. TRIF and STING interacted directly, through their carboxy-terminal domains, to promote STING dimerization, intermembrane translocation, and signaling. Herpes simplex virus (HSV), which triggers the STING signaling pathway and is controlled by it, replicated more efficiently in the absence of TRIF, and HSV-infected TRIF−/− mice displayed pronounced pathology. Our results indicate that defective STING signaling may be responsible for the observed genetic association between TRIF mutations and herpes simplex encephalitis in patients.

Original languageEnglish
Pages (from-to)329-341
Number of pages13
JournalCell Host and Microbe
Volume20
Issue number3
DOIs
StatePublished - Sep 14 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Inc.

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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