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Bacterial genotoxins induce T cell senescence
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National Kapodistrian University of Athens, Athens, Greece.
Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National Kapodistrian University of Athens, Athens, Greece.
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2021 (English)In: Cell Reports, E-ISSN 2211-1247, Vol. 35, no 10, article id 109220Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2021. Vol. 35, no 10, article id 109220
Keywords [en]
ATM, bacteria, cytolethal distending toxin, DNA damage, genotoxins, inflammation, senescence, senescence-associated secretory phenotype, T cells, typhoid toxin
National Category
Immunology
Identifiers
URN: urn:nbn:se:umu:diva-186361DOI: 10.1016/j.celrep.2021.109220ISI: 000659894300012PubMedID: 34107253Scopus ID: 2-s2.0-85107392013OAI: oai:DiVA.org:umu-186361DiVA, id: diva2:1581683
Funder
Novo Nordisk, NNF14OC0012345Swedish Cancer Society, CAN 2017/315Swedish Research Council, 2018-02521Cancerforskningsfonden i Norrland, AMP 17-884The Kempe Foundations, JCK-1826Available from: 2021-07-23 Created: 2021-07-23 Last updated: 2024-01-17Bibliographically approved

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Frisan, Teresa

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Umeå Centre for Microbial Research (UCMR)Department of Molecular Biology (Faculty of Medicine)Department of Molecular Biology (Faculty of Science and Technology)
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