title: Toll-like receptor downstream signaling.
abstract: The family of Toll-like receptors (TLRs) senses conserved structures found in a broad range of pathogens, causing innate immune responses that include the production of inflammatory cytokines, chemokines and interferons. The signal transduction is initiated from the Toll/interleukin-1 receptor (TIR) domain of TLRs after pathogen recognition. Almost all TLRs use a TIR-containing adapter MyD88 to activate a common signaling pathway that results in the activation of NF-kappaB to express cytokine genes relevant to inflammation. Recently, three further TIR-containing adapters have been identified and shown to selectively interact with several TLRs. In particular, activation of the TRIF-dependent pathway confers antiviral responses by inducing anti-viral genes including that encoding interferon-beta. Taken together, these results indicate that the interaction between individual TLRs and the different combinations of adapters directs appropriate responses against distinct pathogens.
authors.affiliation: ERATO, Japan Science and Technology Agency, Osaka, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Kawai
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism; D029721:Drosophila Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D051550:I-kappa B Kinase / Q000502:physiology; D007239:Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D017434:Protein Structure, Tertiary; D017472:Receptors, Interleukin-1 / Q000502:physiology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000737:chemistry / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029721:Drosophila Proteins; D008024:Ligands; C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human