1. Department of Microbiology and Immunology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida 33136, USA
2. These authors contributed equally to this work

Correspondence to: Glen N. Barber Email: gbarber@med.miami.edu

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, 2, 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 (/) 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 genes⁶. 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.

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