2010
DOI: 10.1038/ni.1932
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IFI16 is an innate immune sensor for intracellular DNA

Abstract: The detection of intracellular microbial DNA is critical to an appropriate innate immune response, however current knowledge on how such DNA is sensed is limited. Here we identify IFI16, a PYHIN protein, as an intracellular DNA sensor mediating interferon-β (IFNβ)-induction. IFI16 directly associated with IFNβ-inducing viral DNA motifs. STING, a critical mediator of IFNβ responses to DNA, was recruited to IFI16 after DNA stimulation. Reduction of expression of IFI16, or its murine ortholog p204, by RNA interfe… Show more

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Cited by 1,425 publications
(1,753 citation statements)
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References 42 publications
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“…On the contrary, dsDNA sensing by IFI16 is length dependent [2], with dsDNA fragments of 150 base pairs reportedly being favourable for the formation of an optimal binding cluster of approximately ten IFI16 protomers [47]. In order to bind stimulatory dsDNA, the HIN domains of IFI16 associate with both DNA strands across both the major and minor strands, in keeping with the requirement of dsDNA rather than ssDNA for the initiation of signalling from IFI16 [2,41]. While both HIN domains of IFI16 can associate with dsDNA, the HINb domain possesses a stronger DNA binding affinity [2,41].…”
Section: Discovery Of Aim2 As a Dna Receptormentioning
confidence: 98%
See 3 more Smart Citations
“…On the contrary, dsDNA sensing by IFI16 is length dependent [2], with dsDNA fragments of 150 base pairs reportedly being favourable for the formation of an optimal binding cluster of approximately ten IFI16 protomers [47]. In order to bind stimulatory dsDNA, the HIN domains of IFI16 associate with both DNA strands across both the major and minor strands, in keeping with the requirement of dsDNA rather than ssDNA for the initiation of signalling from IFI16 [2,41]. While both HIN domains of IFI16 can associate with dsDNA, the HINb domain possesses a stronger DNA binding affinity [2,41].…”
Section: Discovery Of Aim2 As a Dna Receptormentioning
confidence: 98%
“…Unlike AIM2, IFI16 is most abundant in the nucleus as a result of a NLS present in its Nterminal region [10]. IFI16 was initially identified as a novel DNA sensor using a 70 base pair IFN-b-inducing vaccinia virus dsDNA motif to purify DNA-binding proteins from cytosolic human monocytic extracts [2]. Unlike the DNA sensor TLR9, DNA sensing by IFI16 is independent of GC content and sequence [2].…”
Section: Discovery Of Aim2 As a Dna Receptormentioning
confidence: 99%
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“…Commercial testing confirmed plasmids as endotoxin free in undiluted samples, ruling out LPS stimulation (data not shown). DNA, especially unmethylated CpG DNA, is recognised by TLR9, 10 whereas methylated double-strand DNA can also be recognised by many newly described cytoplasmic PRRs, including Zbp-1, 21 HMGB, 22 Dhx36, 23 Ifi16 (Ifi204) 24 or single-strand DNA by Trex1. 25 RNA variants can be recognised by the retinoic acid-induced gene-like helicase family that includes the 2 0 -5 0 -oligoadenylate synthetase (Oas) subfamily.…”
Section: Go Biological Process Term Mappingmentioning
confidence: 99%