IFI16 is an innate immune sensor for intracellular DNA

Nat Immunol. 2010 Nov;11(11):997-1004. doi: 10.1038/ni.1932. Epub 2010 Oct 3.

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-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).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • DNA, Viral / immunology*
  • DNA-Binding Proteins
  • Herpesvirus 1, Human / immunology
  • Humans
  • Immunity, Innate*
  • Interferon-beta / immunology
  • Interferon-beta / metabolism
  • Intracellular Space / immunology*
  • Membrane Proteins / immunology
  • Mice
  • Monocytes / immunology
  • Nuclear Proteins / immunology*
  • Phosphoproteins / immunology*
  • Signal Transduction

Substances

  • AIM2 protein, human
  • DNA, Viral
  • DNA-Binding Proteins
  • Membrane Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • STING protein, human
  • IFI16 protein, human
  • Interferon-beta