A FADD-dependent innate immune mechanism in mammalian cells

Siddharth Balachandran, Emmanuel Thomas, Glen N Barber

Research output: Contribution to journalArticle

224 Citations (Scopus)

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. 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.

Original languageEnglish
Pages (from-to)401-405
Number of pages5
JournalNature
Volume432
Issue number7015
DOIs
StatePublished - Nov 18 2004

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Interferon Type I
Virus Diseases
Innate Immunity
Phosphotransferases
Interferon Regulatory Factor-3
Toll-Like Receptor 3
Receptor-Interacting Protein Serine-Threonine Kinases
Double-Stranded RNA
Bacterial Infections
Genes
Drosophila
Vertebrates
Cell Death
Viruses
Bacteria
Gene Expression
Proteins
Death Domain

ASJC Scopus subject areas

  • General

Cite this

A FADD-dependent innate immune mechanism in mammalian cells. / Balachandran, Siddharth; Thomas, Emmanuel; Barber, Glen N.

In: Nature, Vol. 432, No. 7015, 18.11.2004, p. 401-405.

Research output: Contribution to journalArticle

Balachandran, Siddharth ; Thomas, Emmanuel ; Barber, Glen N. / A FADD-dependent innate immune mechanism in mammalian cells. In: Nature. 2004 ; Vol. 432, No. 7015. pp. 401-405.
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