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.

Keywords

TRIFTLR3Signal transducing adaptor proteinToll-like receptorTLR4Signal transductionCell biologyInterferon regulatory factorsReceptorTLR7ChemistryBiologyInnate immune systemBiochemistry

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Publication Info

Year
2003
Type
article
Volume
301
Issue
5633
Pages
640-643
Citations
3148
Access
Closed

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Masahiro Yamamoto, Shintaro Sato, Hiroaki Hemmi et al. (2003). Role of Adaptor TRIF in the MyD88-Independent Toll-Like Receptor Signaling Pathway. Science , 301 (5633) , 640-643. https://doi.org/10.1126/science.1087262

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DOI
10.1126/science.1087262