| First Author | Balachandran S | Year | 2004 |
| Journal | Nature | Volume | 432 |
| Issue | 7015 | Pages | 401-5 |
| PubMed ID | 15549108 | Mgi Jnum | J:94554 |
| Mgi Id | MGI:3513484 | Doi | 10.1038/nature03124 |
| Citation | Balachandran S, et al. (2004) A FADD-dependent innate immune mechanism in mammalian cells. Nature 432(7015):401-5 |
| abstractText | 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 (alpha/beta) 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. |
