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- Title
Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway.
- Authors
Yamamoto, Masahiro; Sato, Shintaro; Hemmi, Hiroaki; Hoshino, Katsuaki; Kaisho, Tsuneyasu; Sanjo, Hideki; Takeuchi, Osamu; Sugiyama, Masanaka; Okabe, Masaru; Takeda, Kiyoshi; Akira, Shizuo
- 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.
- Publication
Science (New York, N.Y.), 2003, Vol 301, Issue 5633, p640
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1087262