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PMID:12855817
| Citation |
Yamamoto, M, Sato, S, Hemmi, H, Hoshino, K, Kaisho, T, Sanjo, H, Takeuchi, O, Sugiyama, M, Okabe, M, Takeda, K and Akira, S (2003) Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301:640-3 |
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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)-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. |
| Links |
PubMed Online version:10.1126/science.1087262 |
| Keywords |
Adaptor Proteins, Signal Transducing; Adaptor Proteins, Vesicular Transport/genetics; Adaptor Proteins, Vesicular Transport/physiology; Animals; Antigens, Differentiation/physiology; Cells, Cultured; Cytokines/biosynthesis; DNA-Binding Proteins/metabolism; Dimerization; Embryo, Mammalian; Fibroblasts/metabolism; Gene Expression Regulation; Gene Targeting; Interferon Regulatory Factor-3; Interferon-beta/genetics; Interferon-beta/metabolism; JNK Mitogen-Activated Protein Kinases; Ligands; Lipopolysaccharides/immunology; Lipopolysaccharides/pharmacology; Macrophages, Peritoneal/immunology; Macrophages, Peritoneal/metabolism; Membrane Glycoproteins/metabolism; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases/metabolism; Myeloid Differentiation Factor 88; NF-kappa B/metabolism; Poly I-C/pharmacology; Receptors, Cell Surface/metabolism; Receptors, Immunologic/physiology; Signal Transduction; Toll-Like Receptor 3; Toll-Like Receptor 4; Toll-Like Receptors; Transcription Factors/metabolism |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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