Aminobisphosphonates Synergize with Human Cytomegalovirus To Activate the Antiviral Activity of Vγ9Vδ2 Cells
| Autor: | Suzanne Peyrottes, Eric Champagne, Charline Daguzan, Christian Davrinche, Morgane Moulin, Hanna Kulyk-Barbier |
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| Přispěvatelé: | Centre de Physiopathologie Toulouse Purpan (ex IFR 30 et IFR 150) (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 2 - Sciences et Techniques (UM2), Ecole Nationale Supérieure de Chimie de Montpellier, and Grant Number : Fondation pour la Recherche Medicale Grant [DCM20121225761], Comité d'éthique de l'Inserm (CEI), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Cytotoxicity
Immunologic 0301 basic medicine Human cytomegalovirus lymphocytes bisphosphonate [SDV]Life Sciences [q-bio] Isopentenyl pyrophosphate Cytomegalovirus hiv-infection MESH: T-Lymphocyte Subsets Lymphocyte Activation Virus Replication stimulation [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity chemistry.chemical_compound zoledronic acid T-Lymphocyte Subsets [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Immunology and Allergy Cells Cultured ComputingMilieux_MISCELLANEOUS MESH: Cytokines Diphosphonates MESH: Dendritic Cells Receptors Antigen T-Cell gamma-delta tumor-cells MESH: Mevalonic Acid inhibition 3. Good health MESH: Leukocytes Mononuclear medicine.anatomical_structure [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology Cytomegalovirus Infections Host-Pathogen Interactions Cytokines [SDV.IMM]Life Sciences [q-bio]/Immunology Tumor necrosis factor alpha receptor-gamma delta t-cells MESH: Cells Cultured MESH: Cytomegalovirus replication MESH: Diphosphonates T cell Immunology Mevalonic Acid Biology Cell Line 03 medical and health sciences Antigen MESH: Receptors Antigen T-Cell gamma-delta medicine Humans MESH: Cytotoxicity Immunologic MESH: Lymphocyte Activation MESH: Humans T-cell receptor MESH: Virus Replication MESH: Host-Pathogen Interactions Lymphokine Dendritic Cells MESH: Cytomegalovirus Infections [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy medicine.disease Virology MESH: Cell Line 030104 developmental biology chemistry Cell culture Leukocytes Mononuclear Cancer research [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | Journal of Immunology Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2016, 196 (5), pp.2219-2229. ⟨10.4049/jimmunol.1501661⟩ Journal of Immunology, 2016, 196 (5), pp.2219-2229. ⟨10.4049/jimmunol.1501661⟩ |
| ISSN: | 0022-1767 1550-6606 |
| DOI: | 10.4049/jimmunol.1501661⟩ |
| Popis: | Human V gamma 9V delta 2 T cells are activated through their TCR by neighboring cells producing phosphoantigens. Zoledronate (ZOL) treatment induces intracellular accumulation of the phosphoantigens isopentenyl pyrophosphate and ApppI. Few attempts have been made to use immunomanipulation of V gamma 9V delta 2 lymphocytes in chronic viral infections. Although V gamma 9V delta 2 T cells seem to ignore human CMV (HCMV)-infected cells, we examined whether they can sense HCMV when a TCR stimulus is provided with ZOL. Fibroblasts treated with ZOL activate V gamma 9V delta 2 T cells to produce IFN-gamma but not TNF. Following the same treatment, HCMV-infected fibroblasts stimulate TNF secretion and an increased production of IFN-g, indicating that V gamma 9V delta 2 cells can sense HCMV infection. Increased lymphokine production was observed with most clinical isolates and laboratory HCMV strains, HCMV-permissive astrocytoma, or dendritic cells, as well as "naive" and activated V gamma 9V delta 2 cells. Quantification of intracellular isopentenyl pyrophosphate/ApppI following ZOL treatment showed that HCMV infection boosts their accumulation. This was explained by an increased capture of ZOL and by upregulation of HMG-CoA synthase and reductase transcription. Using an experimental setting where infected fibroblasts were cocultured with gamma delta cells in submicromolar concentrations of ZOL, we show that V gamma 9V delta 2 cells suppressed substantially the release of infectious particles while preserving uninfected cells. V gamma 9V delta 2 cytotoxicity was decreased by HCMV infection of targets whereas anti-IFN-gamma and anti-TNF Abs significantly blocked the antiviral effect. Our experiments indicate that cytokines produced by V gamma 9V delta 2 T cells have an antiviral potential in HCMVinfection. This should lead to in vivo studies to explore the possible antiviral effect of immunostimulation with ZOL in this context. |
| Databáze: | OpenAIRE |
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