Authors
Unterholzner, LeonieKeating, Sinead E.
Baran, Marcin
Horan, Kristy A.
Jensen, Soren B.
Sharma, Shrutie
Sirois, Cherilyn M.
Jin, Tengchuan
Latz, Eicke
Xiao, T. Sam
Fitzgerald, Katherine A.
Paludan, Soren R.
Bowie, Andrew G.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2010-11-05Keywords
AnimalsCell Line
DNA, Viral
Herpesvirus 1, Human
Humans
*Immunity, Innate
Interferon-beta
Intracellular Space
Membrane Proteins
Mice
Monocytes
Nuclear Proteins
Phosphoproteins
Signal Transduction
Immunology and Infectious Disease
Metadata
Show full item recordAbstract
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-beta (IFN-beta). IFI16 directly associated with IFN-beta-inducing viral DNA motifs. STING, a critical mediator of IFN-beta 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-kappaB 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-beta induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs).Source
Nat Immunol. 2010 Nov;11(11):997-1004. Epub 2010 Oct 3. Link to article on publisher's siteDOI
10.1038/ni.1932Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34886PubMed ID
20890285Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/ni.1932