IFI16 is an innate immune sensor for intracellular DNA
Department of Medicine, Division of Infectious Diseases and Immunology
Animals; Cell Line; DNA, Viral; Herpesvirus 1, Human; Humans; *Immunity, Innate; Interferon-beta; Intracellular Space; Membrane Proteins; Mice; Monocytes; Nuclear Proteins; Phosphoproteins; Signal Transduction
Immunology and Infectious Disease
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-beta (IFN-beta). IFI16 directly associated with IFN-beta-inducing viral DNA motifs. STING, a critical mediator of IFN-beta 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-kappaB 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-beta induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs).
DOI of Published Version
Nat Immunol. 2010 Nov;11(11):997-1004. Epub 2010 Oct 3. Link to article on publisher's site
Unterholzner L, Keating SE, Baran M, Horan KA, Jensen SB, Sharma S, Sirois CM, Jin T, Latz E, Xiao T, Fitzgerald KA, Paludan SR, Bowie AG. (2010). IFI16 is an innate immune sensor for intracellular DNA. Infectious Diseases and Immunology Publications. https://doi.org/10.1038/ni.1932. Retrieved from https://escholarship.umassmed.edu/infdis_pp/114