Assembly and Localization of Toll-like Receptor Signalling Complexes

Nat Rev Immunol. 2014 Aug;14(8):546-58. doi: 10.1038/nri3713.

Abstract

Signal transduction by the Toll-like receptors (TLRs) is central to host defence against many pathogenic microorganisms and also underlies a large burden of human disease. Thus, the mechanisms and regulation of signalling by TLRs are of considerable interest. In this Review, we discuss the molecular basis for the recognition of pathogen-associated molecular patterns, the nature of the protein complexes that mediate signalling, and the way in which signals are regulated and integrated at the level of allosteric assembly, post-translational modification and subcellular trafficking of the components of the signalling complexes. These fundamental molecular mechanisms determine whether the signalling output leads to a protective immune response or to serious pathologies such as sepsis. A detailed understanding of these processes at the molecular level provides a rational framework for the development of new drugs that can specifically target pathological rather than protective signalling in inflammatory and autoimmune disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drosophila Proteins / immunology
  • Drosophila melanogaster
  • Humans
  • Immunity, Innate*
  • Myeloid Differentiation Factor 88 / immunology
  • Protein Processing, Post-Translational
  • Protein Transport
  • Receptors, Pattern Recognition / immunology*
  • Signal Transduction / immunology
  • Toll-Like Receptors / immunology*

Substances

  • Drosophila Proteins
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • Receptors, Pattern Recognition
  • Toll-Like Receptors