© 2005 The Japanese Society for Immunology
REVIEW ARTICLE |
Toll-like receptors in innate immunity
1 Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, 2 Department of Host Defense, Research Institute for Microbial Diseases, Osaka University and 3 ERATO, Japan Science and Technology Agency, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan
Corresponding author: S. Akira; E-mail: sakira{at}biken.osaka-u.ac.jp
Functional characterization of Toll-like receptors (TLRs) has established that innate immunity is a skillful system that detects invasion of microbial pathogens. Recognition of microbial components by TLRs initiates signal transduction pathways, which triggers expression of genes. These gene products control innate immune responses and further instruct development of antigen-specific acquired immunity. TLR signaling pathways are finely regulated by TIR domain-containing adaptors, such as MyD88, TIRAP/Mal, TRIF and TRAM. Differential utilization of these TIR domain-containing adaptors provides specificity of individual TLR-mediated signaling pathways. Several mechanisms have been elucidated that negatively control TLR signaling pathways, and thereby prevent overactivation of innate immunity leading to fatal immune disorders. The involvement of TLR-mediated pathways in autoimmune and inflammatory diseases has been proposed. Thus, TLR-mediated activation of innate immunity controls not only host defense against pathogens but also immune disorders.
Keywords: adaptor, innate immunity, signal transduction, TIR domain, Toll-like receptor
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|
|
|
|
|
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|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
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|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
W.-J. Won, M. F. Bachmann, and J. F. Kearney CD36 Is Differentially Expressed on B Cell Subsets during Development and in Responses to Antigen J. Immunol., January 1, 2008; 180(1): 230 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
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|
|
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|
|
|
|
|
|
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|
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|
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|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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