Microbial recognition by Toll-like receptors.
Toll-like receptors (TLRs) sense invasion of microorganisms by detecting microbial components that are conserved among pathogens. Recognition of microbial components by TLRs triggers activation of the innate immune system. Signaling pathways via TLRs originate from conserved cytoplasmic Toll/IL-1 receptor (TIR) domains. Recent accumulating evidence demonstrates that TIR domain-containing adaptors, such as MyD88, TIRAP/Mal, TRIF, and TRAM, regulate TLR-mediated signaling pathways. MyD88 is common to all TLR-mediated pathways, which lead to the production of inflammatory cytokines, whereas TRIF mediates induction of IFN-beta in TLR3 and TLR4 signaling pathways. TIRAP/Mal is implicated in the TLR2- and TLR4-mediated MyD88-dependent signaling pathway. TRAM is specifically involved in the TLR4-mediated TRIF-dependent pathway. Thus, TIR domain-containing adaptors play a pivotal role in TLR signaling pathways, which culminate in pathogen-specific immune responses.
Takeda
Kiyoshi
K
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, ERATO, Japan Science and Technology Corporation, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
Akira
Shizuo
S
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001424:Bacterial Infections / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C470409:TICAM1 protein, human; C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; C074282:translocating chain-associating membrane protein (TRAM)