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

Abstract: 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 caspaseactivated DNAse. In biopsies from H. pylori-positive patients, we observed a correlation of Smac-levels and inflammation. Nonapoptotic 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

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Cell death and differentiation. - 29, 11 (2022) , 2218-2232, ISSN: 1476-5403

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2022
• Urheber: Dörflinger, Benedikt ; Badr, Mohamed Tarek ; Haimovici, Aladin ; Fischer, Lena ; Vier, Juliane ; Metz, Arlena ; Eisele, Bianca ; Bronsert, Peter ; Aumann, Konrad ; Höppner, Jens ; Waguia Kontchou, Collins ; Parui, Ishita ; Weber, Arnim ; Kirschnek, Susanne ; Häcker, Georg

Weitere Informationen

• DOI: 10.1038/s41418-022-01009-9
• URN: urn:nbn:de:bsz:25-freidok-2267825
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 25.03.2025, 13:42 MEZ