IFI16 is an innate immune sensor for intracellular DNA.
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).
Mesh Terms:
Animals, Cell Line, DNA, Viral, DNA-Binding Proteins, Herpesvirus 1, Human, Humans, Immunity, Innate, Interferon-beta, Intracellular Space, Membrane Proteins, Mice, Monocytes, Nuclear Proteins, Phosphoproteins, Signal Transduction
Animals, Cell Line, DNA, Viral, DNA-Binding Proteins, Herpesvirus 1, Human, Humans, Immunity, Innate, Interferon-beta, Intracellular Space, Membrane Proteins, Mice, Monocytes, Nuclear Proteins, Phosphoproteins, Signal Transduction
Nat. Immunol.
Date: Nov. 01, 2010
PubMed ID: 20890285
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