IFI16 is an innate immune sensor for intracellular DNA

Leonie Unterholzner (Lead / Corresponding author), Sinead E Keating, Marcin Baran, Kristy A Horan, Søren B Jensen, Shruti Sharma, Cherilyn M Sirois, Tengchuan Jin, Eicke Latz, T Sam Xiao, Katherine A Fitzgerald, Søren R Paludan, Andrew G Bowie (Lead / Corresponding author)

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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-ß (IFN-ß). IFI16 directly associated with IFN-ß-inducing viral DNA motifs. STING, a critical mediator of IFN-ß 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-?B 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-ß induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs).
    Original languageEnglish
    Pages (from-to)997-1004
    Number of pages8
    JournalNature Immunology
    Volume11
    Issue number11
    DOIs
    Publication statusPublished - Nov 2010

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  • Cite this

    Unterholzner, L., Keating, S. E., Baran, M., Horan, K. A., Jensen, S. B., Sharma, S., Sirois, C. M., Jin, T., Latz, E., Xiao, T. S., Fitzgerald, K. A., Paludan, S. R., & Bowie, A. G. (2010). IFI16 is an innate immune sensor for intracellular DNA. Nature Immunology, 11(11), 997-1004. https://doi.org/10.1038/ni.1932