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

@article{Yamamoto2003RoleOA,
  title={Role of Adaptor TRIF in the MyD88-Independent Toll-Like Receptor Signaling Pathway},
  author={Masahiro Yamamoto and Shintaro Sato and Hiroaki Hemmi and Katsuaki Hoshino and Tsuneyasu Kaisho and Hideki Sanjo and Osamu Takeuchi and Masanaka Sugiyama and Masaru Okabe and Kiyoshi Takeda and Shizuo Akira},
  journal={Science},
  year={2003},
  volume={301},
  pages={640 - 643}
}
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… 

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References

SHOWING 1-10 OF 21 REFERENCES

Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4

The results show that TIRAP has a crucial role in the MyD88-dependent signalling pathway shared by TLR2 and TLR4, and is not specific to TLR3, TLR7 or TLR9 signalling, which is in contrast to previous suggestions.

The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors

TIRAP, an adaptor protein in the TLR signalling pathway, has been identified and shown to function downstream of TLR4 and may account for specificity in the downstream signalling of individual TLRs.

TICAM-1, an adaptor molecule that participates in Toll-like receptor 3–mediated interferon-β induction

This work has identified an alternative adaptor, designated Toll-interleukin 1 receptor domain (TIR)-containing adaptor molecule (TICAM)-1, that can physically bind the TIR domain of TLR3 and activate the IFN-β promoter in response to poly(I):poly(C).

Differential involvement of IFN-beta in Toll-like receptor-stimulated dendritic cell activation.

Toll-like receptor (TLR) can activate dendritic cells (DC) through common signaling pathways requiring a cytoplasmic adapter, MyD88. However, the signaling is differentially regulated among TLR

Cutting Edge: A Novel Toll/IL-1 Receptor Domain-Containing Adapter That Preferentially Activates the IFN-β Promoter in the Toll-Like Receptor Signaling1

Findings suggest that TRIF is involved in the TLR signaling, particularly in the MyD88-independent pathway.

Lipopolysaccharide Stimulates the MyD88-Independent Pathway and Results in Activation of IFN-Regulatory Factor 3 and the Expression of a Subset of Lipopolysaccharide-Inducible Genes1

The characterization of the MyD88-independent pathway via TLR4 is reported, a MyD 88-dependent pathway that is critical to the induction of inflammatory cytokines and a Myd88/TNFR-associated factor 6- independent pathway that regulates induction of IP-10.

Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3

It is shown that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces the activation of NF-κB and the production of type I interferons (IFNs).

Toll-like receptors.

The innate immune system in drosophila and mammals senses the invasion of microorganisms using the family of Toll receptors, stimulation of which initiates a range of host defense mechanisms and there is evidence for additional pathways that mediate TLR ligand-specific biological responses.