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. 2003 Aug 1;301(5633):640-3.
doi: 10.1126/science.1087262. Epub 2003 Jul 10.

Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway

Masahiro Yamamoto  1 , Shintaro Sato, Hiroaki Hemmi, Katsuaki Hoshino, Tsuneyasu Kaisho, Hideki Sanjo, Osamu Takeuchi, Masanaka Sugiyama, Masaru Okabe, Kiyoshi Takeda, Shizuo Akira
Affiliations

Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway

Masahiro Yamamoto et al. Science. .

Abstract

Stimulation of Toll-like receptors (TLRs) triggers activation of a common MyD88-dependent signaling pathway as well as a MyD88-independent pathway that is unique to TLR3 and TLR4 signaling pathways leading to interferon (IFN)-beta production. Here we disrupted the gene encoding a Toll/IL-1 receptor (TIR) domain-containing adaptor, TRIF. TRIF-deficient mice were defective in both TLR3- and TLR4-mediated expression of IFN-beta and activation of IRF-3. Furthermore, inflammatory cytokine production in response to the TLR4 ligand, but not to other TLR ligands, was severely impaired in TRIF-deficient macrophages. Mice deficient in both MyD88 and TRIF showed complete loss of nuclear factor kappa B activation in response to TLR4 stimulation. These findings demonstrate that TRIF is essential for TLR3- and TLR4-mediated signaling pathways facilitating mammalian antiviral host defense.

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