Bacterial genotoxins induce T cell senescence
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Bacterial genotoxins induce T cell senescence. / Mathiasen, Sarah L.; Gall-Mas, Laura; Pateras, Ioannis S.; Theodorou, Sofia D.P.; Namini, Martin R.J.; Hansen, Morten B.; Martin, Océane C.B.; Vadivel, Chella Krishna; Ntostoglou, Konstantinos; Butter, Deborah; Givskov, Michael; Geisler, Carsten; Akbar, Arne N.; Gorgoulis, Vassilis G.; Frisan, Teresa; Ødum, Niels; Krejsgaard, Thorbjørn.
In: Cell Reports, Vol. 35, No. 10, 109220, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Bacterial genotoxins induce T cell senescence
AU - Mathiasen, Sarah L.
AU - Gall-Mas, Laura
AU - Pateras, Ioannis S.
AU - Theodorou, Sofia D.P.
AU - Namini, Martin R.J.
AU - Hansen, Morten B.
AU - Martin, Océane C.B.
AU - Vadivel, Chella Krishna
AU - Ntostoglou, Konstantinos
AU - Butter, Deborah
AU - Givskov, Michael
AU - Geisler, Carsten
AU - Akbar, Arne N.
AU - Gorgoulis, Vassilis G.
AU - Frisan, Teresa
AU - Ødum, Niels
AU - Krejsgaard, Thorbjørn
N1 - Publisher Copyright: © 2021 The Authors
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - ATM
KW - bacteria
KW - cytolethal distending toxin
KW - DNA damage
KW - genotoxins
KW - inflammation
KW - senescence
KW - senescence-associated secretory phenotype
KW - T cells
KW - typhoid toxin
U2 - 10.1016/j.celrep.2021.109220
DO - 10.1016/j.celrep.2021.109220
M3 - Journal article
C2 - 34107253
AN - SCOPUS:85107392013
VL - 35
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 10
M1 - 109220
ER -
ID: 272067633