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The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling

O’Neill LAJ, Bowie AG2007Nature reviews. ImmunologyReview
10.1038/nri2079PubMed
Immune/Innate

Abstract

Signalling by Toll-like receptors (TLRs) involves five adaptor proteins known as MyD88, MAL, TRIF, TRAM and SARM. Recent insights have revealed additional functions for MyD88 apart from NF-kappaB activation, including activation of the transcription factors IRF1, IRF5 and IRF7, and also a role outside the TLRs in interferon-gamma signalling. Biochemical information on MAL and TRAM has shown that both act as bridging adaptors, with MAL recruiting MyD88 to TLR2 and TLR4, and TRAM recruiting TRIF to TLR4 to allow for IRF3 activation. Finally, the function of the fifth adaptor, SARM, has been revealed, which negatively regulates TRIF. These new insights allow for a detailed description of the function of the five TIR-domain-containing adaptors in the initiation of TLR signalling.

Cited By (3)

  • Toll-Like Receptors as a Therapeutic Target in the Era of ImmunotherapiesFrontiers in Cell and Developmental Biology · 2021
  • Population genetic tools for dissecting innate immunity in humansNature reviews. Immunology · 2013
  • TLR9 responses of B cells are repressed by intravenous immunoglobulin through the recruitment of phosphataseJournal of Autoimmunity · 2011

References (2)

  • Fas ligation on macrophages enhances IL-1R1-Toll-like receptor 4 signaling and promotes chronic inflammationNature Immunology · 2004
  • MyD88-mediated stabilization of interferon-γ-induced cytokine and chemokine mRNANature Immunology · 2006

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