Cooperation between MyD88 and TRIF pathways in TLR synergy via IRF5 activation

Xinshou Ouyang, Hideo Negishi, Rie Takeda, Yasuyuki Fujita, Tadatsugu Taniguchi, Kenya Honda

Research output: Contribution to journalArticlepeer-review

96 Citations (Scopus)


Signaling by Toll-like receptors (TLRs) is central to evoking innate immunity, wherein each TLR is activated by distinct pathogen-derived agonists. It has been shown previously that TLR signaling occurs in synergy when certain TLR agonist combinations simultaneously activate immune cells. This synergism may constitute a mechanism critical to ensuring the effective activation of the immune system by multiple TLR activating molecules associated with a given pathogen; however, its underlying mechanism(s) remain unclarified. Here, we provide evidence that TLRs utilizing the MyD88 adaptor selectively cooperate with those utilizing the TRIF adaptor for synergistic induction of a set of target genes, and that this synergism is abrogated in cells lacking either MyD88 or TRIF. Moreover, we also provide evidence that this TLR synergy is mediated, at least in part, by activation of the transcription factor interferon regulatory factor 5 (IRF5). Thus, our findings offer a mechanistic insight into TLR synergy, revealing the hitherto unknown cross talk between the MyD88 and TRIF pathways for a robust TLR-mediated activation of the immune system.

Original languageEnglish
Pages (from-to)1045-1051
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number4
Publication statusPublished - 2007 Mar 23
Externally publishedYes


  • IRF
  • MyD88
  • Synergy
  • TLR
  • TRIF

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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