The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
DNA-PK is a DNA sensor for IRF-3-dependent innate immunity
Open accessAbstract
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.
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Cites
Neutrophil Extracellular Traps Kill Bacteria
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“Similar results have been reported previously (Stetson and Medzhitov, 2006; Ishii et al., 2006; Ishikawa et al., 2009) and in a similar manner confirmed that cytoplasmic DNA sensing in fibroblasts is independent of TLRs (Ishii et al.”
BackgroundResultInfluentialMitochondrial DNA that escapes from autophagy causes inflammation and heart failure
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“Trex1 deficiency or mutation, on the other hand, is associated with systemic lupus erythematosus (SLE), chilblain lupus and the human disease Aicardi-Goutières syndrome (AGS) (Lee-Kirsch et al., 2007a, 2007b; Stetson et al., 2008) and in this case inflammation is initiated from non-haematopoietic cells via a STING-dep…”
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Cutting edge: Ku70 is a novel cytosolic DNA sensor that induces type III rather than type I IFN
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Cited by
Mitotic progression following DNA damage enables pattern recognition within micronuclei
Harding, S. M., Benci, J. L., Irianto, J., Discher, D. E., Minn, A. J., & Greenberg, R. A. (2017) · Nature · doi:10.1038/nature23470 · Cited by 1,508
Aicardi–Goutières syndrome and the type I interferonopathies
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The cGAS-STING Defense Pathway and Its Counteraction by Viruses
Ma, Z., & Damania, B. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.01.010 · Cited by 445
Wang, Q., Liu, X., Cui, Y., Tang, Y., Chen, W., Li, S., Yu, H., Pan, Y., & Wang, C. (2014) · Immunity · doi:10.1016/j.immuni.2014.11.011 · Cited by 358
Metadata
- Authors
- Ferguson, B. J., Mansur, D. S., Peters, N. E., Ren, H., & Smith, G. L.
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2012-12-18
- Volume
- 1
- Pages
- e00047-e00047
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W2158542519
- Cited by
- 404
- References
- 10
- FWCI
- 10.23
- Type
- journal article
- Language
- en
- Open access
- gold
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- Ferguson, B. J., Mansur, D. S., Peters, N. E., Ren, H., & Smith, G. L. (2012). DNA-PK is a DNA sensor for IRF-3-dependent innate immunity. eLife. https://doi.org/10.7554/elife.00047
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