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Pattern recognition receptors

DNA damage drives detection

Nature Reviews Immunology volume 13, pages 704–705 (2013)Cite this article

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A series of experiments showed that ultraviolet irradiation of DNA has a dose-dependent effect on type I interferon (IFN) production by immune and non-immune cells exposed to this DNA in mice and humans. The authors observed the generation of intracellular reactive oxygen species (ROS) in cells exposed to ultraviolet radiation, which resulted in a dose-dependent increase in oxidative damage to DNA, as measured by 8-hydroxyguanine (8-OHG), which is the oxidation product of guanine. The 8-OHG content of DNA correlated with its ability to stimulate IFN production.

The authors went on to investigate how ROS production by myeloid cells might affect the detection of ingested pathogen DNA. The type I IFN response of mouse dendritic cells that had been transfected with bacterial or viral genomic DNA was enhanced in a dose-dependent manner when the DNA was first incubated with hydrogen peroxide. So, in addition to directly damaging pathogens, ROS production might also indirectly facilitate their immune detection.

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References

  1. Gehrke, N. et al. Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing. Immunity http:dx.doi.org/10.1016/j.immuni.2013.08.004 (2013)

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  1. Kirsty Minton
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Broz, P. & Monack, D. M. Newly described pattern recognition receptors team up against intracellular pathogens. Nature Rev. Immunol. 13, 551–565 (2013)

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Minton, K. DNA damage drives detection. Nat Rev Immunol 13, 704–705 (2013). https://doi.org/10.1038/nri3539

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