Bacterial genotoxins induce T cell senescence
| Autor: | Niels Ødum, Laura Gall-Mas, Konstantinos Ntostoglou, Deborah Butter, Sarah L. Mathiasen, Carsten Geisler, Sofia D.P. Theodorou, Michael Givskov, Teresa Frisan, Morten Bagge Hansen, Martin R J Namini, Thorbjørn Krejsgaard, Ioannis S. Pateras, Chella Krishna Vadivel, Vassilis G. Gorgoulis, Océane C.B. Martin, Arne N. Akbar |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Senescence senescence Cytolethal distending toxin DNA damage T cell T-Lymphocytes Immunology T cells typhoid toxin Inflammation Biology medicine.disease_cause General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine medicine Humans bacteria Cellular Senescence Host (biology) Pathogenic bacteria biology.organism_classification Cell biology 030104 developmental biology medicine.anatomical_structure inflammation ATM Immunologi senescence-associated secretory phenotype genotoxins medicine.symptom cytolethal distending toxin 030217 neurology & neurosurgery Bacteria DNA Damage Mutagens |
| Zdroj: | 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, vol. 35, no. 10, 109220 . https://doi.org/10.1016/j.celrep.2021.109220 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2021.109220 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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