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Role of Adaptor TRIF in the MyD88-Independent Toll-like Receptor Signaling Pathway

Masahiro Yamamoto, Shintaro Sato, Hiroaki Hemmi, Katsuaki Hoshino, Tsuneyasu Kaisho, Hideki Sanjo, Osamu Takeuchi, Masanaka Sugiyama, Masaru Okabe, Kiyoshi Takeda and Shizuo Akira
Science
New Series, Vol. 301, No. 5633 (Aug. 1, 2003), pp. 640-643
Stable URL: http://www.jstor.org/stable/3834886
Page Count: 4
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Role of Adaptor TRIF in the MyD88-Independent Toll-like Receptor Signaling Pathway
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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)-β 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-β 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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