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

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.

SUBMITTER: Wang X

PROVIDER: S-EPMC5026396 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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

Wang Xin X Majumdar Tanmay T Kessler Patricia P Ozhegov Evgeny E Zhang Ying Y Chattopadhyay Saurabh S Barik Sailen S Sen Ganes C GC

Cell host & microbe 20160901 3

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. H ...[more]

PMID: 27631700

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