TLR signaling.
The Toll-like receptor (TLR) family plays an instructive role in innate immune responses against microbial pathogens, as well as the subsequent induction of adaptive immune responses. TLRs recognize specific molecular patterns found in a broad range of microbial pathogens such as bacteria and viruses, triggering inflammatory and antiviral responses and dendritic cell maturation, which result in the eradication of invading pathogens. Individual TLRs interact with different combinations of adapter proteins and activate various transcription factors such as nuclear factor (NF)-kappaB, activating protein-1 and interferon regulatory factors, driving a specific immune response. This review outlines the recent advances in our understanding of TLR-signaling pathways and their roles in immune responses. Further, we also discuss a new concept of TLR-independent mechanisms for recognition of microbial pathogens.
Kawai
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Exploratory Research for Advanced Technology, Japan Science and Technology Agency, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
Akira
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D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D053487:DEAD-box RNA Helicases; D004330:Drosophila; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D050835:Interferon Regulatory Factors / Q000378:metabolism; D000072640:Interferon-Induced Helicase, IFIH1; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020365:RNA Helicases / Q000378:metabolism; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D000097905:Roundabout Proteins
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D053487:DEAD-box RNA Helicases; D050835:Interferon Regulatory Factors; D000072640:Interferon-Induced Helicase, IFIH1; D008565:Membrane Proteins; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D020365:RNA Helicases; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D018808:Transcription Factor AP-1; C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins; C452815:IFIH1 protein, human