TRIF-dependent TLR signaling, its functions in host defense and inflammation, and its potential as a therapeutic target

M. Obayed Ullah, Matthew J. Sweet, Ashley Mansell, Stuart Kellie, Bostjan Kobe

Research output: Contribution to journalReview ArticleResearchpeer-review

42 Citations (Scopus)

Abstract

Toll/IL-1R domain-containing adaptor-inducing IFN-β (TRIF)-dependent signaling is required for TLR-mediated production of type-I IFN and several other proinflammatory mediators. Various pathogens target the signaling molecules and transcriptional regulators acting in the TRIF pathway, thus demonstrating the importance of this pathway in host defense. Indeed, the TRIF pathway contributes to control of both viral and bacterial pathogens through promotion of inflammatory mediators and activation of antimicrobial responses. TRIF signaling also has both protective and pathologic roles in several chronic inflammatory disease conditions, as well as an essential function in wound-repair processes. Here, we review our current understanding of the regulatory mechanisms that control TRIF-dependent TLR signaling, the role of the TRIF pathway in different infectious and noninfectious pathologic states, and the potential for manipulating TRIF-dependent TLR signaling for therapeutic benefit.

Original languageEnglish
Pages (from-to)27-45
Number of pages19
JournalJournal of leukocyte biology
Volume100
Issue number1
DOIs
Publication statusPublished - 1 Jul 2016

Keywords

  • adaptor protein
  • innate immunity
  • pattern recognition receptor

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