TLRs, NLRs and RLRs: a trinity of pathogen sensors that co-operate in innate immunity

Trends Immunol. 2006 Aug;27(8):352-7. doi: 10.1016/ Epub 2006 Jun 27.


Significant advances in our understanding of innate immunity have been made following the identification of three families of pathogen sensors: Toll-like receptors (TLRs), NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs). Members of the TLR family recognize bacteria, viruses, fungi and protozoa; NLRs with known functions detect bacteria, and RLRs are anti-viral. It is likely that interplay between these families ensures the efficient co-ordination of innate immune responses, through either synergistic or co-operative signalling. Important interactions occur between TLRs and certain NLRs for inducing the pro-inflammatory cytokine interleukin (IL)-1beta. TLRs induce pro-IL-1beta production and prime NLR-containing multi-protein complexes, termed "inflammasomes", to respond to bacterial products and products of damaged cells. This results in caspase-1 activation and the subsequent processing of pro-IL-1beta to its active form. In this article, we hypothesize that during the first phase of the host response to infection, an important interplay occurs between these families, providing a substantial combinatorial repertoire in innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / physiology*
  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / physiology*
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / physiology*
  • Humans
  • Immunity, Innate*
  • Infections / immunology*
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Signal Transduction
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / physiology*


  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • NLRP1 protein, human
  • Toll-Like Receptors
  • Ddx58 protein, mouse
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases