%0 Journal Article
%T Bacterial genotoxins induce T cell senescence.
%A Mathiasen SL
%A Gall-Mas L
%A Pateras IS
%A Theodorou SDP
%A Namini MRJ
%A Hansen MB
%A Martin OCB
%A Vadivel CK
%A Ntostoglou K
%A Butter D
%A Givskov M
%A Geisler C
%A Akbar AN
%A Gorgoulis VG
%A Frisan T
%A Ødum N
%A Krejsgaard T
%J Cell Rep
%V 35
%N 10
%D Jun 2021 8
%M 34107253
暂无%R 10.1016/j.celrep.2021.109220
%X 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.