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Updated: Jul 5, 2025
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Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo
Published on: September 18, 2014
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DNA-PKcs is required for cGAS/STING-dependent viral DNA sensing in human cells.
Dayana B Hristova1, Marisa Oliveira1, Emma Wagner1
1Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Iscience
|January 25, 2024
Summary
DNA-dependent protein kinase (DNA-PK) is crucial for the interferon response to viral DNA. This finding impacts understanding of innate immunity, autoinflammation, and anti-tumour immunity by highlighting DNA-PK
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- Intracellular pattern recognition receptors (PRRs) detect viral nucleic acids to trigger interferon responses.
- Sensing of intracellular DNA is vital for antiviral immunity, autoinflammation, and anti-tumour immunity.
- DNA-sensing PRRs activate interferon regulatory factor (IRF)-dependent type I interferon (IFN-I) transcription.
Purpose of the Study:
- To investigate the role of DNA-dependent protein kinase (DNA-PK) in DNA-triggered interferon responses.
- To elucidate the mechanism by which DNA-PK contributes to cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) signaling.
Main Methods:
- Stimulation of human cells with exogenous DNA.
- Infection of human cells with DNA viruses.
- Assessment of IFN-I responses and the role of DNA-PK, cGAS, and STING.
Main Results:
- DNA-dependent protein kinase (DNA-PK) is essential for IFN-I responses triggered by exogenous DNA.
- DNA-PK is also critical for IFN-I production during DNA virus infection.
- The study demonstrates DNA-PK's essential function in cGAS- and STING-dependent IFN-I pathways.
Conclusions:
- DNA-PK plays a vital role in the innate immune sensing of DNA, including viral DNA.
- DNA-PK is a key component of the cGAS-STING pathway, essential for antiviral type I interferon production.
- These findings have implications for understanding inflammatory diseases and cancer immunotherapy.
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