Myeloid differentiation factor 88-dependent and -independent pathways in Toll-like receptor signaling

被引：130
作者：
Akira, S
Hoshino, K
机构：
[1] Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Osaka 565087, Japan
[2] SORST Japan Sci & Technol, Osaka, Japan
来源：
JOURNAL OF INFECTIOUS DISEASES | 2003年 / 187卷
关键词：
D O I：
10.1086/374749
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Toll-like receptors (TLRs) play an essential role in the detection of invading pathogens in the body. Individual TLRs recognize distinct components derived from pathogens, which is followed by cytokine production. The TLR family harbors extracellular leucine-rich repeat domains and a cytoplasmic domain that is homologous to that of the interleukin (IL)-1 receptor (IL-1R) family. After stimulation, TLR recruits IL-1R-associated kinase via adaptor myeloid differentiation factor 88 (MyD88) and induces activation of NF-kappaB and mitogen-activated protein kinases. Cytokine production in response to each TLR ligand is completely abrogated in MyD88-deficient cells, which indicates that MyD88 is an essential shared signaling molecule in the IL-1R/Toll family. The TLR4 signal has an MyD88-independent pathway that is involved in induction of type I interferons (IFNs) and IFN-inducible genes via IFN regulatory factor-3 activation. A recently identified adaptor molecule, Toll-IL receptor domain-containing adaptor protein/MyD88 adaptor-like, may participate in the MyD88-independent pathway.
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页码：S356 / S363
页数：8
相关论文
共 62 条
[1]   Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function [J].
Adachi, O ;
Kawai, T ;
Takeda, K ;
Matsumoto, M ;
Tsutsui, H ;
Sakagami, M ;
Nakanishi, K ;
Akira, S .
IMMUNITY, 1998, 9 (01) :143-150
[2]   Toll-like receptors in the induction of the innate immune response [J].
Aderem, A ;
Ulevitch, RJ .
NATURE, 2000, 406 (6797) :782-787
[3]   Toll-like receptors: critical proteins linking innate and acquired immunity [J].
Akira, S ;
Takeda, K ;
Kaisho, T .
NATURE IMMUNOLOGY, 2001, 2 (08) :675-680
[4]   Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3 [J].
Alexopoulou, L ;
Holt, AC ;
Medzhitov, R ;
Flavell, RA .
NATURE, 2001, 413 (6857) :732-738
[5]   Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2 [J].
Aliprantis, AO ;
Yang, RB ;
Mark, MR ;
Suggett, S ;
Devaux, B ;
Radolf, JD ;
Klimpel, GR ;
Godowski, P ;
Zychlinsky, A .
SCIENCE, 1999, 285 (5428) :736-739
[6]   Toll-like receptor 2-mediated NF-κB activation requires a RacI-dependent pathway [J].
Arbibe, L ;
Mira, JP ;
Teusch, N ;
Kline, L ;
Guha, M ;
Mackman, N ;
Godowski, PJ ;
Ulevitch, RJ ;
Knaus, UG .
NATURE IMMUNOLOGY, 2000, 1 (06) :533-540
[7]   Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors [J].
Brightbill, HD ;
Libraty, DH ;
Krutzik, SR ;
Yang, RB ;
Belisle, JT ;
Bleharski, JR ;
Maitland, M ;
Norgard, MV ;
Plevy, SE ;
Smale, ST ;
Brennan, PJ ;
Bloom, BR ;
Godowski, PJ ;
Modlin, RL .
SCIENCE, 1999, 285 (5428) :732-736
[8]   Cooperation of toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein:: Role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling [J].
Bulut, Y ;
Faure, E ;
Thomas, L ;
Equils, O ;
Arditi, M .
JOURNAL OF IMMUNOLOGY, 2001, 167 (02) :987-994
[9]   Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor [J].
Burns, K ;
Clatworthy, J ;
Martin, L ;
Martinon, F ;
Plumpton, C ;
Maschera, B ;
Lewis, A ;
Ray, K ;
Tschopp, J ;
Volpe, F .
NATURE CELL BIOLOGY, 2000, 2 (06) :346-351
[10]  
Byrd-Leifer CA, 2001, EUR J IMMUNOL, V31, P2448, DOI 10.1002/1521-4141(200108)31:8&lt
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