IFI16 is an innate immune sensor for intracellular DNA

By Leonie Unterholzner, Sinéad E Keating, Marcin Baran, K. Horan, S. Jensen, Shrutie Sharma, C. Sirois, T. Jin, T. Xiao, Katherine A. Fitzgerald and 2 more. Nature Immunology, 2010

1,697 citations recorded by the source corpus.

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).

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/651e5150015cd0dab49a1fed43f2f54db65214da

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Citations in the corpus

Structural mechanism of cytosolic DNA sensing by cGAS (2013, positive): “It will also be important to investigate additional requirements for efficient DNA sensing in vivo , because while shorter dsDNA molecules can stimulate cGAS Mab21 in vitro , DNA > 50mer is required for efficient IFN stimulation in vivo 14,19 .”
IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi sarcoma associated herpesvirus infection (2011, background): “Recently, Unterholzner et al (Unterholzner et al., 2010) have shown that in response to herpes simplex virus type 1 (HSV-1) infection, IFI16 mediates the induction of transcription factors IRF3 and NF-κB as well as their target genes.”
Inflammation and its role in age-related macular degeneration (2016, background): “In contrast to other DNA sensors, such as DAI (DNA-dependent activator of IFN-regulatory factors) and one other PYHIN protein, IFI16 (interferon gamma-inducible protein 16), AIM2 does not mediate the type I IFN production [58, 59].”
Cyclic [G(2′,5′)pA(3′,5′)p] Is the Metazoan Second Messenger Produced by DNA-Activated Cyclic GMP-AMP Synthase (2013, positive): “, 2009) and IFI16 (interferon-inducible protein 16) (Unterholzner et al., 2010).”
Innate Immune Pattern Recognition: A Cell Biological Perspective (2015, neutral): “A more diverse set of functions has been attributed to a second member, IFI16, including the activation of STINGdependent IFN production and inflammasome formation (231, 247).”
Regulation of inflammasome activation (2015, background): “In human, the PYD-containing protein, POP3, interacts with the PYD domain of AIM2 and competes with ASC to inhibit AIM2 inflammasome activation in response to poly(dA:dT), mouse CMV, and modified vaccinia virus Ankara (184).”