New insights into the regulation of signalling by toll-like receptors and nod-like receptors

J Innate Immun. 2010;2(5):406-21. doi: 10.1159/000315469. Epub 2010 May 27.


The activation of Toll-Like receptors (TLRs) and Nod-like receptors (NLRs) triggers intracellular signalling pathways that lead to effector mechanisms in innate immunity and inflammation. The negative regulation of TLR signalling has been extensively studied. Current areas of research include post-transcriptional regulation by miRNA, post-translational regulation by ubiquitination and regulation by splice variants such as MyD88s, TRAM adaptor with GOLD domain and IRAK2 isoforms. The negative regulation of NLR signalling is a relatively new area of research. Examples include a splice variant of NOD2, the ubiquitin editing enzyme A20, pyrin domain-only proteins and caspase recruitment domain-only proteins which all have a negative effect on NOD2 or NLRP3 signalling. A greater understanding of the mechanisms underlying the negative control of TLR and NLR signalling may provide new targets for therapeutic intervention.

Publication types

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

MeSH terms

  • Animals
  • Gene Expression Regulation*
  • Humans
  • Immunity, Innate* / genetics
  • Immunity, Innate* / immunology
  • Inflammation* / genetics
  • Inflammation* / immunology
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Nod2 Signaling Adaptor Protein / genetics
  • Nod2 Signaling Adaptor Protein / metabolism*
  • Signal Transduction*
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism*
  • Ubiquitin / metabolism


  • MicroRNAs
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • Toll-Like Receptors
  • Ubiquitin