TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway

被引：794

作者：

Yamamoto, M

Sato, S

Hemmi, H

Uematsu, S

Hoshino, K

Kaisho, T

Takeuchi, O

Takeda, K

Akira, S ^{[1
]}

机构：

[1] Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Suita, Osaka 5650871, Japan

[2] ERATO, Japan Sci & Technol Corp, Suita, Osaka 5650871, Japan

[3] RIKEN, Res Ctr Allergy & Immunol, Tsurumi Ku, Kanagawa 2300045, Japan

来源：

NATURE IMMUNOLOGY | 2003年 / 4卷 / 11期

关键词：

D O I：

10.1038/ni986

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Recognition of pathogens by Toll-like receptors (TLRs) triggers innate immune responses through signaling pathways mediated by Toll-interleukin 1 receptor (TIR) domain-containing adaptors such as MyD88, TIRAP and TRIF. MyD88 is a common adaptor that is essential for proinflammatory cytokine production, whereas TRIF mediates the MyD88-independent pathway from TLR3 and TLR4. Here we have identified a fourth TIR domain-containing adaptor, TRIF-related adaptor molecule (TRAM), and analyzed its physiological function by gene targeting. TRAM-deficient mice showed defects in cytokine production in response to the TLR4 ligand, but not to other TLR ligands. TLR4- but not TLR3-mediated MyD88-independent interferon-production and activation of signaling cascades were abolished in TRAM-deficient cells. Thus, TRAM provides specificity for the MyD88-independent component of TLR4 signaling.

引用

收藏

页码：1144 / 1150

页数：7

相关论文

共 46 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] Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice [J].

Alexopoulou, L ;

Thomas, V ;

Schnare, M ;

Lobet, Y ;

Anguita, J ;

Schoen, RT ;

Medzhitov, R ;

Fikrig, E ;

Flavell, RA .

NATURE MEDICINE, 2002, 8 (08) :878-884

[3] 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

[4] TIRP, a novel Toll/interleukin-1 receptor (TIR) domain-containing adapter protein involved in TIR signaling [J].

Bin, LH ;

Xu, LG ;

Shu, HB .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (27) :24526-24532

[5] IRF3 mediates a TLR3/TLR4-specific antiviral gene program [J].

Doyle, SE ;

Vaidya, SA ;

O'Connell, R ;

Dadgostar, H ;

Dempsey, PW ;

Wu, TT ;

Rao, G ;

Sun, R ;

Haberland, ME ;

Modlin, RL ;

Cheng, G .

IMMUNITY, 2002, 17 (03) :251-263

[6] IKKε and TBK1 are essential components of the IRF3 signaling pathway [J].

Fitzgerald, KA ;

McWhirter, SM ;

Faia, KL ;

Rowe, DC ;

Latz, E ;

Golenbock, DT ;

Coyle, AJ ;

Liao, SM ;

Maniatis, T .

NATURE IMMUNOLOGY, 2003, 4 (05) :491-496

[7] Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction [J].

Fitzgerald, KA ;

Palsson-McDermott, EM ;

Bowie, AG ;

Jefferies, CA ;

Mansell, AS ;

Brady, G ;

Brint, E ;

Dunne, A ;

Gray, P ;

Harte, MT ;

McMurray, D ;

Smith, DE ;

Sims, JE ;

Bird, TA ;

O'Neill, LAJ .

NATURE, 2001, 413 (6851) :78-83

[8] Oligomerisation of Tube and Pelle leads to nuclear localisation of Dorsal [J].

Grosshans, J ;

Schnorrer, F ;

Nüsslein-Volhard, C .

MECHANISMS OF DEVELOPMENT, 1999, 81 (1-2) :127-138

[9] Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor receptor-associated factor (TRAF)6 [J].

Häcker, H ;

Vabulas, RM ;

Takeuchi, O ;

Hoshino, K ;

Akira, S ;

Wagner, H .

JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (04) :595-600

[10] The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5 [J].

Hayashi, F ;

Smith, KD ;

Ozinsky, A ;

Hawn, TR ;

Yi, EC ;

Goodlett, DR ;

Eng, JK ;

Akira, S ;

Underhill, DM ;

Aderem, A .

NATURE, 2001, 410 (6832) :1099-1103

← 1 2 3 4 5 →