A FADD-dependent innate immune mechanism in mammalian cells

被引：243

作者：

Balachandran, Siddharth ^{[1
]}

Thomas, Emmanuel ^{[1
]}

Barber, Glen N. ^{[1
]}

机构：

[1] Dept. of Microbiology and Immunology, Sylvester Compreh. Cancer Center, Univ. of Miami School of Medicine, Miami

来源：

Nature | 2004年 / 432卷 / 7015期

基金：

加拿大健康研究院;

关键词：

Immune response - Pathogens;

D O I：

10.1038/nature03124

中图分类号：

学科分类号：

摘要：

Vertebrate innate immunity provides a first line of defence against pathogens such as viruses and bacteria. Viral infection activates a potent innate immune response, which can be triggered by double-stranded (ds)RNA produced during viral replication. Here, we report that mammalian cells lacking the death-domain-containing protein FADD are defective in intracellular dsRNA-activated gene expression, including production of type I (α/β) interferons, and are thus very susceptible to viral infection. The signalling pathway incorporating FADD is largely independent of Toll-like receptor 3 and the dsRNA-dependent kinase PKR, but seems to require receptor interacting protein 1 as well as Tank-binding kinase 1-mediated activation of the transcription factor IRF-3. The requirement for FADD in mammalian host defence is evocative of innate immune signalling in Drosophila, in which a FADD-dependent pathway responds to bacterial infection by activating the transcription of antimicrobial genes. These data therefore suggest the existence of a conserved pathogen recognition pathway in mammalian cells that is essential for the optimal induction of type I interferons and other genes important for host defence.

引用

页码：401 / 405

页数：4

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