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).
Unterholzner
Leonie
L
School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.
Keating
Sinead E
SE
Baran
Marcin
M
Horan
Kristy A
KA
Jensen
Søren B
SB
Sharma
Shruti
S
Sirois
Cherilyn M
CM
Jin
Tengchuan
T
Latz
Eicke
E
Xiao
T Sam
TS
Fitzgerald
Katherine A
KA
Paludan
Søren R
SR
Bowie
Andrew G
AG
D000818:Animals; D002460:Cell Line; D004279:DNA, Viral / Q000276:immunology*; D004268:DNA-Binding Proteins; D018259:Herpesvirus 1, Human / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D016899:Interferon-beta / Q000276:immunology / Q000378:metabolism; D042541:Intracellular Space / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology; D009687:Nuclear Proteins / Q000276:immunology*; D010750:Phosphoproteins / Q000276:immunology*; D015398:Signal Transduction; D000099197:STING Protein
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D016899:Interferon-beta; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C410167:AIM2 protein, human; C532857:STING1 protein, human; D000099197:STING Protein; C076700:IFI16 protein, human