| First Author | Ferguson BJ | Year | 2012 |
| Journal | Elife | Volume | 1 |
| Pages | e00047 | PubMed ID | 23251783 |
| Mgi Jnum | J:197877 | Mgi Id | MGI:5494816 |
| Doi | 10.7554/eLife.00047 | Citation | Ferguson BJ, et al. (2012) DNA-PK is a DNA sensor for IRF-3-dependent innate immunity. Elife 1:e00047 |
| abstractText | 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. |
