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Nat Immunol. 2010 Nov;11(11):997-1004. doi: 10.1038/ni.1932. Epub 2010 Oct 3.

IFI16 is an innate immune sensor for intracellular DNA.

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1
School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.

Abstract

The detection of intracellular microbial DNA is critical to appropriate innate immune responses; however, knowledge of how such DNA is sensed is limited. Here we identify IFI16, a PYHIN protein, as an intracellular DNA sensor that mediates the induction of interferon-β (IFN-β). IFI16 directly associated with IFN-β-inducing viral DNA motifs. STING, a critical mediator of IFN-β responses to DNA, was recruited to IFI16 after DNA stimulation. Lowering the expression of IFI16 or its mouse ortholog p204 by RNA-mediated interference inhibited gene induction and activation of the transcription factors IRF3 and NF-κB induced by DNA and herpes simplex virus type 1 (HSV-1). IFI16 (p204) is the first PYHIN protein to our knowledge shown to be involved in IFN-β induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs).

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PMID:
20890285
PMCID:
PMC3142795
DOI:
10.1038/ni.1932
[Indexed for MEDLINE]
Free PMC Article
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