1. Human Dendritic Cells Infected with the Nonpathogenic Mopeia Virus Induce Stronger T-Cell Responses than Those Infected with Lassa Virus
- Author
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Sylvain Baize, Marion Russier, Stéphanie Reynard, Delphine Pannetier, Vincent Deubel, Alexandra Journeaux, Noël Tordo, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), This work was supported by the Délégation Générale pour l'Armement (0034053). D.P. is a fellow recipient of the Délégation Générale pour l'Armement., Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), and MATEO, MATHIEU
- Subjects
CD4-Positive T-Lymphocytes ,Enzyme-Linked Immunospot Assay ,Cellular immunity ,MESH: Flow Cytometry ,Lymphocyte Activation ,medicine.disease_cause ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,0302 clinical medicine ,MESH: Reverse Transcriptase Polymerase Chain Reaction ,Cytotoxic T cell ,Lassa fever ,Cells, Cultured ,[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,MESH: Cytokines ,0303 health sciences ,MESH: Dendritic Cells ,Reverse Transcriptase Polymerase Chain Reaction ,MESH: CD4-Positive T-Lymphocytes ,MESH: Enzyme-Linked Immunosorbent Assay ,MESH: Lassa virus ,MESH: Arenaviruses, Old World ,Flow Cytometry ,3. Good health ,medicine.anatomical_structure ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,MESH: Immunologic Memory ,Cytokines ,MESH: Cells, Cultured ,T cell ,Immunology ,Enzyme-Linked Immunosorbent Assay ,Biology ,Microbiology ,Virus ,MESH: Coculture Techniques ,03 medical and health sciences ,MESH: Cell Proliferation ,Virology ,medicine ,Humans ,Lassa virus ,MESH: Lymphocyte Activation ,[SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity ,Cell Proliferation ,030304 developmental biology ,MESH: Humans ,Arenavirus ,Dendritic Cells ,Dendritic cell ,medicine.disease ,biology.organism_classification ,Coculture Techniques ,Insect Science ,Pathogenesis and Immunity ,MESH: Enzyme-Linked Immunospot Assay ,Arenaviruses, Old World ,Immunologic Memory ,MESH: T-Lymphocytes, Cytotoxic ,T-Lymphocytes, Cytotoxic ,030215 immunology - Abstract
The events leading to death in severe cases of Lassa fever (LF) are unknown. Fatality seems to be linked to high viremia and immunosuppression, and cellular immunity, rather than neutralizing antibodies, appears to be essential for survival. We previously compared Lassa virus (LV) with its genetically close but nonpathogenic homolog Mopeia virus (MV), which was used to model nonfatal LF. We showed that strong and early activation of antigen-presenting cells (APC) may play a crucial role in controlling infection. Here we developed an in vitro model of dendritic-cell (DC)-T-cell coculture in order to characterize human T-cell responses induced by MV- or LV-infected DCs. Our results show very different responses to infection with LV and MV. MV strongly and durably stimulated CD8 + and CD4 + T cells, showing early and high activation, a strong proliferative response, and acquisition of effector and memory phenotypes. Furthermore, robust and functional CD4 + and CD8 + cytotoxic T lymphocytes (CTL) were generated. LV, however, induced only weak memory responses. Thus, this study allows an improved understanding of the pathogenesis and immune mechanisms involved in the control of human LV.
- Published
- 2011
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