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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 (Engelska)Ingår i: Cell Reports, E-ISSN 2211-1247, Vol. 35, nr 10, artikel-id 109220Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
Elsevier, 2021. Vol. 35, nr 10, artikel-id 109220
Nyckelord [en]
ATM, bacteria, cytolethal distending toxin, DNA damage, genotoxins, inflammation, senescence, senescence-associated secretory phenotype, T cells, typhoid toxin
Nationell ämneskategori
Immunologi
Identifikatorer
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
Forskningsfinansiär
Novo Nordisk, NNF14OC0012345Cancerfonden, CAN 2017/315Vetenskapsrådet, 2018-02521Cancerforskningsfonden i Norrland, AMP 17-884Kempestiftelserna, JCK-1826Tillgänglig från: 2021-07-23 Skapad: 2021-07-23 Senast uppdaterad: 2024-01-17Bibliografiskt granskad

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Frisan, Teresa

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Umeå Centre for Microbial Research (UCMR)Institutionen för molekylärbiologi (Medicinska fakulteten)Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet)
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