Bacterial genotoxins induce T cell senescence

Research output: Contribution to journalJournal articleResearchpeer-review


Several types of pathogenic bacteria produce genotoxins that induce DNA damage in host cells. Accumulating evidence suggests that a central function of these genotoxins is to dysregulate the host's immune response, but the underlying mechanisms remain unclear. To address this issue, we investigated the effects of the most widely expressed bacterial genotoxin, the cytolethal distending toxin (CDT), on T cells—the key mediators of adaptive immunity. We show that CDT induces premature senescence in activated CD4 T cells in vitro and provide evidence suggesting that infection with genotoxin-producing bacteria promotes T cell senescence in vivo. Moreover, we demonstrate that genotoxin-induced senescent CD4 T cells assume a senescence-associated secretory phenotype (SASP) which, at least partly, is orchestrated by the ATM-p38 signaling axis. These findings provide insight into the immunomodulatory properties of bacterial genotoxins and uncover a putative link between bacterial infections and T cell senescence.

Original languageEnglish
Article number109220
JournalCell Reports
Issue number10
Publication statusPublished - 2021

Bibliographical note

Publisher Copyright:
© 2021 The Authors

    Research areas

  • ATM, bacteria, cytolethal distending toxin, DNA damage, genotoxins, inflammation, senescence, senescence-associated secretory phenotype, T cells, typhoid toxin

Number of downloads are based on statistics from Google Scholar and

No data available

ID: 272067633