Περίληψη:
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 ATMp38 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.
Συγγραφείς:
Mathiasen, Sarah L.
Gall-Mas, Laura
Pateras, Ioannis S. and
Theodorou, Sofia D. P.
Namini, Martin R. J.
Hansen, Morten B.
and Martin, Oceane C. B.
Vadivel, Chella Krishna
Ntostoglou,
Konstantinos
Butter, Deborah
Givskov, Michael
Geisler,
Carsten
Akbar, Arne N.
Gorgoulis, Vassilis G.
Frisan, Teresa
and Odum, Niels
Krejsgaard, Thorbjorn
