Mitochondria supply sub-lethal signals for cytokine secretion and DNA-damage in H. pylori infection.

Autor: Dörflinger B; Faculty of Medicine, Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Freiburg, Germany., Badr MT; Faculty of Medicine, Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Freiburg, Germany., Haimovici A; Faculty of Medicine, Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Freiburg, Germany., Fischer L; Faculty of Medicine, Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Freiburg, Germany., Vier J; Faculty of Medicine, Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Freiburg, Germany., Metz A; Faculty of Medicine, Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Freiburg, Germany., Eisele B; Faculty of Medicine, Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Freiburg, Germany., Bronsert P; Faculty of Medicine, Institute for Surgical Pathology, Medical Center, University of Freiburg, Freiburg, Germany.; Comprehensive Cancer Center Freiburg, Medical Center, University of Freiburg, Freiburg, Germany., Aumann K; Faculty of Medicine, Institute for Surgical Pathology, Medical Center, University of Freiburg, Freiburg, Germany.; Comprehensive Cancer Center Freiburg, Medical Center, University of Freiburg, Freiburg, Germany.; Center for Pathology Allgäu, Kempten Allgäu, Germany., Höppner J; Comprehensive Cancer Center Freiburg, Medical Center, University of Freiburg, Freiburg, Germany.; Department of Surgery, University Medical Center Schleswig-Holstein, Lübeck, Germany., Waguia Kontchou C; Faculty of Medicine, Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Freiburg, Germany., Parui I; Faculty of Medicine, Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Freiburg, Germany., Weber A; Faculty of Medicine, Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Freiburg, Germany., Kirschnek S; Faculty of Medicine, Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Freiburg, Germany., Häcker G; Faculty of Medicine, Institute of Medical Microbiology and Hygiene, Medical Center, University of Freiburg, Freiburg, Germany. georg.haecker@uniklinik-freiburg.de.; BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany. georg.haecker@uniklinik-freiburg.de.
Jazyk: angličtina
Zdroj: Cell death and differentiation [Cell Death Differ] 2022 Nov; Vol. 29 (11), pp. 2218-2232. Date of Electronic Publication: 2022 May 03.
DOI: 10.1038/s41418-022-01009-9
Abstrakt: The bacterium Helicobacter pylori induces gastric inflammation and predisposes to cancer. H. pylori-infected epithelial cells secrete cytokines and chemokines and undergo DNA-damage. We show that the host cell's mitochondrial apoptosis system contributes to cytokine secretion and DNA-damage in the absence of cell death. H. pylori induced secretion of cytokines/chemokines from epithelial cells, dependent on the mitochondrial apoptosis machinery. A signalling step was identified in the release of mitochondrial Smac/DIABLO, which was required for alternative NF-κB-activation and contributed to chemokine secretion. The bacterial cag-pathogenicity island and bacterial muropeptide triggered mitochondrial host cell signals through the pattern recognition receptor NOD1. H. pylori-induced DNA-damage depended on mitochondrial apoptosis signals and the caspase-activated DNAse. In biopsies from H. pylori-positive patients, we observed a correlation of Smac-levels and inflammation. Non-apoptotic cells in these samples showed evidence of caspase-3-activation, correlating with phosphorylation of the DNA-damage response kinase ATM. Thus, H. pylori activates the mitochondrial apoptosis pathway to a sub-lethal level. During infection, Smac has a cytosolic, pro-inflammatory role in the absence of apoptosis. Further, DNA-damage through sub-lethal mitochondrial signals is likely to contribute to mutagenesis and cancer development.
(© 2022. The Author(s).)
Databáze: MEDLINE
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