The Caspase-Activated DNase drives inflammation and contributes to defense against viral infection

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Abstract: Mitochondria react to infection with sub-lethal signals in the apoptosis pathway. Mitochondrial signals can be inflammatory but mechanisms are only partially understood. We show that activation of the caspase-activated DNase (CAD) mediates mitochondrial pro-inflammatory functions and substantially contributes to host defense against viral infection. In cells lacking CAD, the pro-inflammatory activity of sub-lethal signals was reduced. Experimental activation of CAD caused transient DNA-damage and a pronounced DNA damage response, involving major kinase signaling pathways, NF-κB and cGAS/STING, driving the production of interferon, cytokines/chemokines and attracting neutrophils. The transcriptional response to CAD-activation was reminiscent of the reaction to microbial infection. CAD-deficient cells had a diminished response to viral infection. Influenza virus infected CAD-deficient mice displayed reduced inflammation in lung tissue, higher viral titers and increased weight loss. Thus, CAD links the mitochondrial apoptosis system and cell death caspases to host defense. CAD-driven DNA damage is a physiological element of the inflammatory response to infection

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch
Notes
Cell death and differentiation. - 31, 7 (2024) , 924-937, ISSN: 1476-5403

Event
Veröffentlichung
(where)
Freiburg
(who)
Universität
(when)
2024
Creator

DOI
10.1038/s41418-024-01320-7
URN
urn:nbn:de:bsz:25-freidok-2497544
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
25.03.2025, 1:55 PM CET

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Time of origin

  • 2024

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