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

Harvard

Mathiasen, SL, Gall-Mas, L, Pateras, IS, Theodorou, SDP, Namini, MRJ, Hansen, MB, Martin, OCB, Vadivel, CK, Ntostoglou, K, Butter, D, Givskov, M, Geisler, C, Akbar, AN, Gorgoulis, VG, Frisan, T, Ødum, N & Krejsgaard, T 2021, 'Bacterial genotoxins induce T cell senescence', Cell Reports, vol. 35, no. 10, 109220. https://doi.org/10.1016/j.celrep.2021.109220

APA

Mathiasen, S. L., Gall-Mas, L., Pateras, I. S., Theodorou, S. D. P., Namini, M. R. J., Hansen, M. B., Martin, O. C. B., Vadivel, C. K., Ntostoglou, K., Butter, D., Givskov, M., Geisler, C., Akbar, A. N., Gorgoulis, V. G., Frisan, T., Ødum, N., & Krejsgaard, T. (2021). Bacterial genotoxins induce T cell senescence. Cell Reports, 35(10), [109220]. https://doi.org/10.1016/j.celrep.2021.109220

Vancouver

Mathiasen SL, Gall-Mas L, Pateras IS, Theodorou SDP, Namini MRJ, Hansen MB et al. Bacterial genotoxins induce T cell senescence. Cell Reports. 2021;35(10). 109220. https://doi.org/10.1016/j.celrep.2021.109220

Author

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. / Bacterial genotoxins induce T cell senescence. In: Cell Reports. 2021 ; Vol. 35, No. 10.

Bibtex

@article{de7fce0b77bb47bdb88e01f5d0739ca0,
title = "Bacterial genotoxins induce T cell senescence",
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.",
keywords = "ATM, bacteria, cytolethal distending toxin, DNA damage, genotoxins, inflammation, senescence, senescence-associated secretory phenotype, T cells, typhoid toxin",
author = "Mathiasen, {Sarah L.} and Laura Gall-Mas and Pateras, {Ioannis S.} and Theodorou, {Sofia D.P.} and Namini, {Martin R.J.} and Hansen, {Morten B.} and Martin, {Oc{\'e}ane C.B.} and Vadivel, {Chella Krishna} and Konstantinos Ntostoglou and Deborah Butter and Michael Givskov and Carsten Geisler and Akbar, {Arne N.} and Gorgoulis, {Vassilis G.} and Teresa Frisan and Niels {\O}dum and Thorbj{\o}rn Krejsgaard",
note = "Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
doi = "10.1016/j.celrep.2021.109220",
language = "English",
volume = "35",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "10",

}

RIS

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