8 results on '"Namini, Martin R. J."'
Search Results
2. Bacterial genotoxins induce T cell senescence
- Author
-
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
- 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 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.
- Published
- 2021
3. Cellular Interactions and Inflammation in the Pathogenesis of Cutaneous T-Cell Lymphoma
- Author
-
Stolearenco, Veronica, primary, Namini, Martin R. J., additional, Hasselager, Siri S., additional, Gluud, Maria, additional, Buus, Terkild B., additional, Willerslev-Olsen, Andreas, additional, Ødum, Niels, additional, and Krejsgaard, Thorbjørn, additional
- Published
- 2020
- Full Text
- View/download PDF
4. The Bacterial Toxin CNF1 Induces Activation and Maturation of Human Monocyte-Derived Dendritic Cells
- Author
-
Gall-Mas, Laura, Fabbri, Alessia, Namini, Martin R J, Givskov, Michael, Fiorentini, Carla, Krejsgaard, Thorbjørn, Gall-Mas, Laura, Fabbri, Alessia, Namini, Martin R J, Givskov, Michael, Fiorentini, Carla, and Krejsgaard, Thorbjørn
- Abstract
Cytotoxic necrotizing factor 1 (CNF1) is a bacterial protein toxin primarily expressed by pathogenic Escherichia coli strains, causing extraintestinal infections. The toxin is believed to enhance the invasiveness of E. coli by modulating the activity of Rho GTPases in host cells, but it has interestingly also been shown to promote inflammation, stimulate host immunity and function as a potent immunoadjuvant. The mechanisms underlying the immunostimulatory properties of CNF1 are, however, poorly characterized, and little is known about the direct effects of the toxin on immune cells. Here, we show that CNF1 induces expression of maturation markers on human immature monocyte-derived dendritic cells (moDCs) without compromising cell viability. Consistent with the phenotypic maturation, CNF1 further triggered secretion of proinflammatory cytokines and increased the capacity of moDCs to stimulate proliferation of allogenic naïve CD4+ T cells. A catalytically inactive form of the toxin did not induce moDC maturation, indicating that the enzymatic activity of CNF1 triggers immature moDCs to undergo phenotypic and functional maturation. As the maturation of dendritic cells plays a central role in initiating inflammation and activating the adaptive immune response, the present findings shed new light on the immunostimulatory properties of CNF1 and may explain why the toxin functions as an immunoadjuvant.
- Published
- 2018
5. Staphylococcus aureusinduces drug resistance in cancer T cells in Sézary syndrome
- Author
-
Vadivel, Chella Krishna, Willerslev-Olsen, Andreas, Namini, Martin R. J., Zeng, Ziao, Yan, Lang, Danielsen, Maria, Gluud, Maria, Pallesen, Emil M. H., Wojewoda, Karolina, Osmancevic, Amra, Hedebo, Signe, Chang, Yun-Tsan, Lindahl, Lise M., Koralov, Sergei B., Geskin, Larisa J., Bates, Susan E., Iversen, Lars, Litman, Thomas, Bech, Rikke, Wobser, Marion, Guenova, Emmanuella, Kamstrup, Maria R., Ødum, Niels, and Buus, Terkild B.
- Abstract
•Enterotoxins from S aureusbacteria induce drug resistance in primary malignant T cells in SS.•Targeting bacteria, their toxins, and downstream signaling pathways in malignant T cells abrogate the induction of drug resistance.
- Published
- 2024
- Full Text
- View/download PDF
6. Keratinocytes Present Staphylococcus aureus Enterotoxins and Promote Malignant and Nonmalignant T Cell Proliferation in Cutaneous T-Cell Lymphoma.
- Author
-
Zeng Z, Vadivel CK, Gluud M, Namini MRJ, Yan L, Ahmad S, Hansen MB, Coquet J, Mustelin T, Koralov SB, Bonefeld CM, Woetmann A, Geisler C, Guenova E, Kamstrup MR, Litman T, Gjerdrum LR, Buus TB, and Ødum N
- Abstract
Cutaneous T-cell lymphoma is characterized by malignant T cells proliferating in a unique tumor microenvironment dominated by keratinocytes (KCs). Skin colonization and infection by Staphylococcus aureus are a common cause of morbidity and are suspected of fueling disease activity. In this study, we show that expression of HLA-DRs, high-affinity receptors for staphylococcal enterotoxins (SEs), by KCs correlates with IFN-γ expression in the tumor microenvironment. Importantly, IFN-γ induces HLA-DR, SE binding, and SE presentation by KCs to malignant T cells from patients with Sézary syndrome and malignant and nonmalignant T-cell lines derived from patients with Sézary syndrome and mycosis fungoides. Likewise, preincubation of KCs with supernatant from patient-derived SE-producing S aureus triggers proliferation in malignant T cells and cytokine release (including IL-2), when cultured with nonmalignant T cells. This is inhibited by pretreatment with engineered bacteriophage S aureus-specific endolysins. Furthermore, alteration in the HLA-DR-binding sites of SE type A and small interfering RNA-mediated knockdown of Jak3 and IL-2Rγ block induction of malignant T-cell proliferation. In conclusion, we show that upon exposure to patient-derived S aureus and SE, KCs stimulate IL-2Rγ/Jak3-dependent proliferation of malignant and nonmalignant T cells in an environment with nonmalignant T cells. These findings suggest that KCs in the tumor microenvironment play a key role in S aureus-mediated disease activity in cutaneous T-cell lymphoma., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
7. Bacterial genotoxins induce T cell senescence.
- Author
-
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, and Krejsgaard T
- Subjects
- Humans, Cellular Senescence genetics, DNA Damage genetics, Mutagens metabolism, T-Lymphocytes metabolism
- 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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
8. The Bacterial Toxin CNF1 Induces Activation and Maturation of Human Monocyte-Derived Dendritic Cells.
- Author
-
Gall-Mas L, Fabbri A, Namini MRJ, Givskov M, Fiorentini C, and Krejsgaard T
- Subjects
- Adjuvants, Immunologic chemistry, Bacterial Toxins genetics, Bacterial Toxins pharmacology, Cell Survival drug effects, Dendritic Cells immunology, Escherichia coli chemistry, Escherichia coli pathogenicity, Escherichia coli Proteins genetics, Escherichia coli Proteins pharmacology, Humans, Inflammation immunology, Inflammation pathology, Monocytes drug effects, Monocytes immunology, rho GTP-Binding Proteins genetics, Adjuvants, Immunologic pharmacology, Bacterial Toxins chemistry, Dendritic Cells drug effects, Escherichia coli Proteins chemistry, Inflammation drug therapy
- Abstract
Cytotoxic necrotizing factor 1 (CNF1) is a bacterial protein toxin primarily expressed by pathogenic Escherichia coli strains, causing extraintestinal infections. The toxin is believed to enhance the invasiveness of E. coli by modulating the activity of Rho GTPases in host cells, but it has interestingly also been shown to promote inflammation, stimulate host immunity and function as a potent immunoadjuvant. The mechanisms underlying the immunostimulatory properties of CNF1 are, however, poorly characterized, and little is known about the direct effects of the toxin on immune cells. Here, we show that CNF1 induces expression of maturation markers on human immature monocyte-derived dendritic cells (moDCs) without compromising cell viability. Consistent with the phenotypic maturation, CNF1 further triggered secretion of proinflammatory cytokines and increased the capacity of moDCs to stimulate proliferation of allogenic naïve CD4+ T cells. A catalytically inactive form of the toxin did not induce moDC maturation, indicating that the enzymatic activity of CNF1 triggers immature moDCs to undergo phenotypic and functional maturation. As the maturation of dendritic cells plays a central role in initiating inflammation and activating the adaptive immune response, the present findings shed new light on the immunostimulatory properties of CNF1 and may explain why the toxin functions as an immunoadjuvant.
- Published
- 2018
- Full Text
- View/download PDF
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