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, Leonie; Keating, Sinead E.; Baran, Marcin; Horan, Kristy A.; Jensen, Soren B.; Sharma, Shrutie; Sirois, Cherilyn M.; Jin, Tengchuan; Latz, Eicke; Xiao, T. Sam; Fitzgerald, Katherine A.; Paludan, Soren R.; and Bowie, Andrew G., "IFI16 is an innate immune sensor for intracellular DNA" (2010). Infectious Diseases and Immunology Publications and Presentations. 114.