TLRs, NLRs and RLRs: a trinity of pathogen sensors that co-operate in innate immunity.
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.
Creagh
Emma M
EM
School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland. ecreagh@tcd.ie
O'Neill
Luke A J
LA
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D007239:Infections / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D000070576:NLR Proteins; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000070576:NLR Proteins; C427903:NLRP1 protein, human; D051193:Toll-Like Receptors; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases