IRF3 mediates a TLR3/TLR4-specific antiviral gene program

被引：814

作者：

Doyle, SE

Vaidya, SA

O'Connell, R

Dadgostar, H

Dempsey, PW

Wu, TT

Rao, G

Sun, R

Haberland, ME

Modlin, RL

Cheng, G ^{[1
]}

机构：

[1] Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, MSTP Grad Program, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, AIDS Inst, Los Angeles, CA 90095 USA

[7] Univ Calif Los Angeles, Dept Med, Div Cardiol, Los Angeles, CA 90095 USA

[8] Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90095 USA

[9] Univ Calif Los Angeles, Dept Med, Div Dermatol, Los Angeles, CA 90095 USA

[10] Affymetrix Inc, Santa Clara, CA 95051 USA

来源：

IMMUNITY | 2002年 / 17卷 / 03期

关键词：

D O I：

10.1016/S1074-7613(02)00390-4

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 [免疫学];

摘要：

We have identified a subset of genes that is specifically induced by stimulation of TLR3 or TLR4 but not by TLR2 or TLR9. Further gene expression analyses established that upregulation of several primary response genes was dependent on NF-kappaB, commonly activated by several TLRs, and interferon regulatory factor 3 (IRF3), which was found to confer TLR3/TLR4 specificity. Also identified was a group of secondary response genes which are part of an autocrine/paracrine loop activated by the primary response gene product, interferon beta (IFNbeta). Selective activation of the TLR3/TLR4-IRF3 pathway potently inhibited viral replication. These results suggest that TLR3 and TLR4 have evolutionarily diverged from other TLRs to activate IRF3, which mediates a specific gene program responsible for innate antiviral responses.

引用

页码：251 / 263

页数：13

共 55 条

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