Chemical Tools for Studying TLR Signaling Dynamics

Cell Chem Biol. 2017 Jul 20;24(7):801-812. doi: 10.1016/j.chembiol.2017.05.022. Epub 2017 Jun 22.

Abstract

The detection of infectious pathogens is essential for the induction of antimicrobial immune responses. The innate immune system detects a wide array of microbes using a limited set of pattern-recognition receptors (PRRs). One family of PRRs with a central role in innate immunity are the Toll-like receptors (TLRs). Upon ligation, these receptors initiate signaling pathways culminating in the release of pro-inflammatory cytokines and/or type I interferons (IFN-I). In recent years, it has become evident that the specific subcellular location and timing of TLR activation affect signaling outcome. The subtlety of this signaling has led to a growing demand for chemical tools that provide the ability to conditionally control TLR activation. In this review, we survey current models for TLR signaling in time and space, discuss how chemical tools have contributed to our understanding of TLR ligands, and describe how they can aid further elucidation of the dynamic aspects of TLR signaling.

Keywords: Toll-like receptor; innate immunity; photo-deprotection; signaling dynamics.

Publication types

  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Humans
  • Immunity, Innate
  • Interferon Type I / metabolism
  • Ligands
  • Lipopeptides / chemistry
  • Lipopeptides / metabolism
  • Lipopeptides / pharmacology
  • Molecular Dynamics Simulation
  • NF-kappa B / metabolism
  • Receptors, Pattern Recognition / metabolism
  • Signal Transduction* / drug effects
  • Toll-Like Receptors / chemistry
  • Toll-Like Receptors / metabolism*

Substances

  • Interferon Type I
  • Ligands
  • Lipopeptides
  • NF-kappa B
  • Pam2CSK4 lipopeptide
  • Receptors, Pattern Recognition
  • Toll-Like Receptors