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Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
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TIRAP, TRAM, and Toll-Like Receptors: The Untold Story

Valérie Lannoy1, Anthony Côté-Biron1, Claude Asselin1

  • 1Department of Immunology and Cell Biology, Cancer Research Institute, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada.

Mediators of Inflammation
|March 17, 2023
PubMed

Insights

Toll-like receptors (TLRs) use adaptor proteins like MyD88, TIRAP, and TRAM to activate the innate immune system. This review highlights the underappreciated roles of TIRAP and TRAM in TLR signaling pathways.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Toll-like receptors (TLRs) are key pattern recognition receptors (PRRs) in innate immunity.
  • TLRs sense microbial components and initiate immune responses via signaling pathways.
  • MyD88 adaptor protein is crucial for most TLR-induced pro-inflammatory cytokine production.

Purpose of the Study:

  • To review the essential roles of adaptor proteins in Toll-like receptor signaling.
  • To emphasize the underappreciated contributions of TIRAP and TRAM adaptors.
  • To highlight the necessity of multiple adaptors for robust TLR function.

Main Methods:

  • Literature review of studies on TLR signaling pathways.
  • Analysis of data concerning MyD88, TIRAP, and TRAM adaptor protein functions.
  • Synthesis of findings on TLR-mediated immune responses.

Main Results:

  • MyD88 is essential for most TLRs, except TLR3, in cytokine induction.
  • TIRAP (Toll-Interleukin-1 Receptor Domain Containing Adaptor Protein) is critical for TLR2 and TLR4 signaling.
  • TRAM (TRIF-Related Adaptor Molecule) is required for MyD88-independent TLR4 signaling.

Conclusions:

  • Full TLR signaling and immune responses depend on multiple adaptor proteins, not just MyD88.
  • TIRAP and TRAM play indispensable roles in mediating TLR-induced cellular functions.
  • Understanding these adaptors is crucial for comprehending innate immune regulation.

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