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DNA-stimulated cell death: implications for host defence, inflammatory diseases and cancer

Nature Reviews Immunology volume 19, pages 141–153 (2019)Cite this article

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Abstract

The immune system detects disturbances in homeostasis that occur during infection, sterile tissue damage and cancer. This initiates immune responses that seek to eliminate the trigger of immune activation and to re-establish homeostasis. At the same time, these mechanisms can also play a crucial role in the progression of disease. The occurrence of DNA in the cytosol constitutes a potent trigger for the innate immune system, governing the production of key inflammatory cytokines such as type I interferons and IL-1β. More recently, it has become clear that cytosolic DNA also triggers other biological responses, including various forms of programmed cell death. In this article, we review the emerging literature on the pathways governing DNA-stimulated cell death and the current knowledge on how these processes shape immune responses to exogenous and endogenous challenges.

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Fig. 1: Hallmark cytokine responses induced by DNA-sensing pattern recognition receptors.
Fig. 2: Cytoplasmic DNA activates a broad range of stress responses.
Fig. 3: Pathways in DNA-stimulated cell death.
Fig. 4: Role of DNA-stimulated PCD in pathology and host protection.

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Acknowledgements

S.R.P. is funded by the European Research Council (ERC-AdG ENVISION; 786602), the Novo Nordisk Foundation (NNF18OC0030274) and the Lundbeck Foundation (R198-2015-171 and R268-2016-3927); V.H. is funded by the European Research Council (ERC-CoG GENESIS; 647858) and the German Research Foundation (DFG) (CRC/Transregio 237; CRC 1335; SPP 1923).

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Nature Reviews Immunology thanks the anonymous reviewer(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Department of Biomedicine, University of Aarhus, Aarhus, Denmark

    Søren R. Paludan & Line S. Reinert

  2. Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    Søren R. Paludan

  3. Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany

    Veit Hornung

  4. Center for Integrated Protein Science (CIPSM), Ludwig-Maximilians-Universität München, Munich, Germany

    Veit Hornung

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Glossary

ER-phagy

Selective autophagy of the endoplasmic reticulum (ER); it serves the purpose of ensuring turnover of the ER to retain function of the organelle.

Micronuclei

DNA-containing extra-nuclear bodies that often form in response to DNA damage.

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Paludan, S.R., Reinert, L.S. & Hornung, V. DNA-stimulated cell death: implications for host defence, inflammatory diseases and cancer. Nat Rev Immunol 19, 141–153 (2019). https://doi.org/10.1038/s41577-018-0117-0

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