| | |  | | | | Record from Web of Science® | | | | | | |
| A FADD-dependent innate immune mechanism in mammalian cells |
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| Author(s): Balachandran S, Thomas E, Barber GN |
| Source: NATURE Volume: 432 Issue: 7015 Pages: 401-405 Published: NOV 18 2004 |
| Times Cited: 109 References: 30 |
| Abstract: 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(1-3). Here, we report that mammalian cells lacking the death-domain-containing protein FADD(4,5) are defective in intracellular dsRNA-activated gene expression, including production of type I (a/b) 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(6). 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Barber, GN (reprint author), Univ Miami, Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA |
Addresses:
1. Univ Miami, Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA
2. Univ Miami, Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 871UX |
| ISSN: 0028-0836 |
| DOI: 10.1038/nature03124 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |