Back to Search
Start Over
DNA-PK is a DNA sensor for IRF-3-dependent innate immunity.
- Source :
-
ELife [Elife] 2012 Dec 18; Vol. 1, pp. e00047. Date of Electronic Publication: 2012 Dec 18. - Publication Year :
- 2012
-
Abstract
- Innate immunity is the first immunological defence against pathogens. During virus infection detection of nucleic acids is crucial for the inflammatory response. Here we identify DNA-dependent protein kinase (DNA-PK) as a DNA sensor that activates innate immunity. We show that DNA-PK acts as a pattern recognition receptor, binding cytoplasmic DNA and triggering the transcription of type I interferon (IFN), cytokine and chemokine genes in a manner dependent on IFN regulatory factor 3 (IRF-3), TANK-binding kinase 1 (TBK1) and stimulator of interferon genes (STING). Both cells and mice lacking DNA-PKcs show attenuated cytokine responses to both DNA and DNA viruses but not to RNA or RNA virus infection. DNA-PK has well-established functions in the DNA repair and V(D)J recombination, hence loss of DNA-PK leads to severe combined immunodeficiency (SCID). However, we now define a novel anti-microbial function for DNA-PK, a finding with implications for host defence, vaccine development and autoimmunity.DOI:http://dx.doi.org/10.7554/eLife.00047.001.
- Subjects :
- Animals
Cytokines biosynthesis
Cytokines immunology
DNA Repair immunology
DNA, Viral metabolism
DNA-Activated Protein Kinase deficiency
DNA-Activated Protein Kinase genetics
DNA-Binding Proteins deficiency
DNA-Binding Proteins genetics
Embryo, Mammalian
Fibroblasts immunology
Fibroblasts virology
Herpesvirus 1, Human immunology
Influenza A virus immunology
Interferon Regulatory Factor-3 genetics
Interferon Type I genetics
Interferon Type I immunology
Membrane Proteins genetics
Membrane Proteins immunology
Mice
Mice, Inbred BALB C
Mice, Knockout
Nuclear Proteins deficiency
Nuclear Proteins genetics
Primary Cell Culture
Protein Serine-Threonine Kinases genetics
Protein Serine-Threonine Kinases immunology
Signal Transduction
V(D)J Recombination
Vaccinia virus immunology
DNA, Viral immunology
DNA-Activated Protein Kinase immunology
DNA-Binding Proteins immunology
Gene Expression Regulation immunology
Immunity, Innate
Interferon Regulatory Factor-3 immunology
Nuclear Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 1
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 23251783
- Full Text :
- https://doi.org/10.7554/eLife.00047