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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    945 Citations (Scopus)


    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
    Issue number11
    Publication statusPublished - Nov 2010

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    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