IFI16 is an innate immune sensor for intracellular DNA

TY - JOUR

T1 - IFI16 is an innate immune sensor for intracellular DNA

AU - Unterholzner, Leonie

AU - Keating, Sinead E

AU - Baran, Marcin

AU - Horan, Kristy A

AU - Jensen, Søren B

AU - Sharma, Shruti

AU - Sirois, Cherilyn M

AU - Jin, Tengchuan

AU - Latz, Eicke

AU - Xiao, T Sam

AU - Fitzgerald, Katherine A

AU - Paludan, Søren R

AU - Bowie, Andrew G

PY - 2010/11

Y1 - 2010/11

N2 - 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-ß (IFN-ß). IFI16 directly associated with IFN-ß-inducing viral DNA motifs. STING, a critical mediator of IFN-ß 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-?B 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-ß induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs).

AB - 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-ß (IFN-ß). IFI16 directly associated with IFN-ß-inducing viral DNA motifs. STING, a critical mediator of IFN-ß 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-?B 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-ß induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs).

UR - https://www.scopus.com/pages/publications/77958140656

U2 - 10.1038/ni.1932

DO - 10.1038/ni.1932

M3 - Article

C2 - 20890285

SN - 1529-2908

VL - 11

SP - 997

EP - 1004

JO - Nature Immunology

JF - Nature Immunology

IS - 11

ER -