IFI16 is an innate immune sensor for intracellular DNA

Unterholzner, Leonie and Keating, Sinead E. and Baran, Marcin and Horan, Kristy A. and Jensen, Søren B. and Sharma, Shruti and Sirois, Cherilyn M. and Jin, Tengchuan and Latz, Eicke and Xiao, T. Sam and Fitzgerald, Katherine A. and Paludan, Søren R. and Bowie, Andrew G. (2010) IFI16 is an innate immune sensor for intracellular DNA. Nature Immunology, 11 (11). pp. 997-1004. ISSN 1529-2908

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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).

Item Type:
Journal Article
Journal or Publication Title:
Nature Immunology
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2400/2403
Subjects:
ID Code:
81771
Deposited By:
Deposited On:
23 Sep 2016 08:02
Refereed?:
Yes
Published?:
Published
Last Modified:
01 Dec 2020 03:59