Bacterial genotoxins induce T cell senescence

Sarah L Mathiasen, Laura Gall-Mas, Ioannis S Pateras, Sofia D P Theodorou, Martin R J Namini, Morten B Hansen, Océane C B Martin, Chella Krishna Vadivel, Konstantinos Ntostoglou, Deborah Butter, Michael Givskov, Carsten Geisler, Arne N Akbar, Vassilis G Gorgoulis, Teresa Frisan, Niels Ødum, Thorbjørn Krejsgaard

20 Citationer (Scopus)

Abstract

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.

OriginalsprogEngelsk
Artikelnummer109220
TidsskriftCell reports
Vol/bind35
Udgave nummer10
Sider (fra-til)109220
DOI
StatusUdgivet - 8 jun. 2021

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