Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
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-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).
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-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).
KW - Animals
KW - Cell Line
KW - DNA, Viral
KW - DNA-Binding Proteins
KW - Herpesvirus 1, Human
KW - Humans
KW - Immunity, Innate
KW - Interferon-beta
KW - Intracellular Space
KW - Membrane Proteins
KW - Mice
KW - Monocytes
KW - Nuclear Proteins
KW - Phosphoproteins
KW - Signal Transduction
U2 - 10.1038/ni.1932
DO - 10.1038/ni.1932
M3 - Journal article
C2 - 20890285
VL - 11
SP - 997
EP - 1004
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 11
ER -