Lassa virus activates myeloid dendritic cells but suppresses their ability to stimulate T cells
Lassa virus (LASV) is responsible for a viral hemorrhagic fever in humans and the death of 3,000 to 5,000 people every year. The immune response to LASV is poorly understood, but type I interferon (IFN-I) and T-cell responses appear to be critical for the host. We studied the response of myeloid den...
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| creator | Schaeffer, Justine Carnec, Xavier Reynard, Stéphanie Mateo, Mathieu Picard, Caroline Pietrosemoli, Natalia Dillies, Marie-Agnès Baize, Sylvain |
| description | Lassa virus (LASV) is responsible for a viral hemorrhagic fever in humans and the death of 3,000 to 5,000 people every year. The immune response to LASV is poorly understood, but type I interferon (IFN-I) and T-cell responses appear to be critical for the host. We studied the response of myeloid dendritic cells (mDC) to LASV, as mDCs are involved in both IFN-I production and T-cell activation. We compared the response of primary human mDCs to LASV and Mopeia virus (MOPV), which is similar to LASV, but non-pathogenic. We showed that mDCs produced substantial amounts of IFN-I in response to both LASV and MOPV. However, only MOPV-infected mDCs were able to activate T cells. More surprisingly, coculture with T cells completely inhibited the activation of LASV-infected mDCs. These differences between LASV and MOPV were mostly due to the LASV nucleoprotein, which has major immunosuppressive properties, but the glycoprotein was also involved. Overall, these results suggest that mDCs may be important for the global response to LASV and play a role in the outcome of Lassa fever. |
| doi_str_mv | 10.1371/journal.ppat.1007430 |
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The immune response to LASV is poorly understood, but type I interferon (IFN-I) and T-cell responses appear to be critical for the host. We studied the response of myeloid dendritic cells (mDC) to LASV, as mDCs are involved in both IFN-I production and T-cell activation. We compared the response of primary human mDCs to LASV and Mopeia virus (MOPV), which is similar to LASV, but non-pathogenic. We showed that mDCs produced substantial amounts of IFN-I in response to both LASV and MOPV. However, only MOPV-infected mDCs were able to activate T cells. More surprisingly, coculture with T cells completely inhibited the activation of LASV-infected mDCs. These differences between LASV and MOPV were mostly due to the LASV nucleoprotein, which has major immunosuppressive properties, but the glycoprotein was also involved. Overall, these results suggest that mDCs may be important for the global response to LASV and play a role in the outcome of Lassa fever.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1007430</identifier><identifier>PMID: 30419076</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Antigens ; Antiviral Agents ; Arenaviridae - immunology ; Arenaviruses ; Bioinformatics ; Biological response modifiers ; Biology and Life Sciences ; Cell activation ; Cell cycle ; Comparative analysis ; Cytotoxicity ; Death ; Dendritic cells ; Dendritic Cells - immunology ; Dendritic Cells - virology ; Fever ; Glycoproteins ; Healthy Volunteers ; Hemorrhage ; Hemorrhagic fever ; Hemorrhagic fevers ; Hemorrhagic Fevers, Viral - virology ; Human behavior ; Human health and pathology ; Humans ; Immune response ; Immune system ; Immunology ; Infections ; Infectious diseases ; Interferon ; Interferon Type I ; Interferon-alpha - metabolism ; Interferon-beta - metabolism ; Lassa fever ; Lassa Fever - virology ; Lassa virus - immunology ; Lassa virus - pathogenicity ; Life Sciences ; Lymphocyte Activation - immunology ; Lymphocyte Activation - physiology ; Lymphocytes ; Lymphocytes T ; Medicine and Health Sciences ; Myeloid Cells - immunology ; Myeloid Cells - virology ; Nucleoproteins - metabolism ; Pathogenesis ; Primary Cell Culture ; Proteins ; RNA polymerase ; T cells ; T-Lymphocytes - immunology ; Viruses</subject><ispartof>PLoS pathogens, 2018-11, Vol.14 (11), p.e1007430-e1007430</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Schaeffer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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immunology</topic><topic>Arenaviruses</topic><topic>Bioinformatics</topic><topic>Biological response modifiers</topic><topic>Biology and Life Sciences</topic><topic>Cell activation</topic><topic>Cell cycle</topic><topic>Comparative analysis</topic><topic>Cytotoxicity</topic><topic>Death</topic><topic>Dendritic cells</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - virology</topic><topic>Fever</topic><topic>Glycoproteins</topic><topic>Healthy Volunteers</topic><topic>Hemorrhage</topic><topic>Hemorrhagic fever</topic><topic>Hemorrhagic fevers</topic><topic>Hemorrhagic Fevers, Viral - virology</topic><topic>Human behavior</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunology</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Interferon</topic><topic>Interferon Type I</topic><topic>Interferon-alpha - metabolism</topic><topic>Interferon-beta - metabolism</topic><topic>Lassa fever</topic><topic>Lassa Fever - virology</topic><topic>Lassa virus - immunology</topic><topic>Lassa virus - pathogenicity</topic><topic>Life Sciences</topic><topic>Lymphocyte Activation - immunology</topic><topic>Lymphocyte Activation - physiology</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Medicine and Health Sciences</topic><topic>Myeloid Cells - immunology</topic><topic>Myeloid Cells - virology</topic><topic>Nucleoproteins - metabolism</topic><topic>Pathogenesis</topic><topic>Primary Cell Culture</topic><topic>Proteins</topic><topic>RNA polymerase</topic><topic>T cells</topic><topic>T-Lymphocytes - immunology</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schaeffer, Justine</creatorcontrib><creatorcontrib>Carnec, Xavier</creatorcontrib><creatorcontrib>Reynard, Stéphanie</creatorcontrib><creatorcontrib>Mateo, Mathieu</creatorcontrib><creatorcontrib>Picard, Caroline</creatorcontrib><creatorcontrib>Pietrosemoli, Natalia</creatorcontrib><creatorcontrib>Dillies, Marie-Agnès</creatorcontrib><creatorcontrib>Baize, Sylvain</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - 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The immune response to LASV is poorly understood, but type I interferon (IFN-I) and T-cell responses appear to be critical for the host. We studied the response of myeloid dendritic cells (mDC) to LASV, as mDCs are involved in both IFN-I production and T-cell activation. We compared the response of primary human mDCs to LASV and Mopeia virus (MOPV), which is similar to LASV, but non-pathogenic. We showed that mDCs produced substantial amounts of IFN-I in response to both LASV and MOPV. However, only MOPV-infected mDCs were able to activate T cells. More surprisingly, coculture with T cells completely inhibited the activation of LASV-infected mDCs. These differences between LASV and MOPV were mostly due to the LASV nucleoprotein, which has major immunosuppressive properties, but the glycoprotein was also involved. 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| subjects | Antigens Antiviral Agents Arenaviridae - immunology Arenaviruses Bioinformatics Biological response modifiers Biology and Life Sciences Cell activation Cell cycle Comparative analysis Cytotoxicity Death Dendritic cells Dendritic Cells - immunology Dendritic Cells - virology Fever Glycoproteins Healthy Volunteers Hemorrhage Hemorrhagic fever Hemorrhagic fevers Hemorrhagic Fevers, Viral - virology Human behavior Human health and pathology Humans Immune response Immune system Immunology Infections Infectious diseases Interferon Interferon Type I Interferon-alpha - metabolism Interferon-beta - metabolism Lassa fever Lassa Fever - virology Lassa virus - immunology Lassa virus - pathogenicity Life Sciences Lymphocyte Activation - immunology Lymphocyte Activation - physiology Lymphocytes Lymphocytes T Medicine and Health Sciences Myeloid Cells - immunology Myeloid Cells - virology Nucleoproteins - metabolism Pathogenesis Primary Cell Culture Proteins RNA polymerase T cells T-Lymphocytes - immunology Viruses |
| title | Lassa virus activates myeloid dendritic cells but suppresses their ability to stimulate T cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T01%3A42%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Lassa%20virus%20activates%20myeloid%20dendritic%20cells%20but%20suppresses%20their%20ability%20to%20stimulate%20T%20cells&rft.jtitle=PLoS%20pathogens&rft.au=Schaeffer,%20Justine&rft.date=2018-11-12&rft.volume=14&rft.issue=11&rft.spage=e1007430&rft.epage=e1007430&rft.pages=e1007430-e1007430&rft.issn=1553-7374&rft.eissn=1553-7374&rft_id=info:doi/10.1371/journal.ppat.1007430&rft_dat=%3Cgale_plos_%3EA564080714%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2251105054&rft_id=info:pmid/30419076&rft_galeid=A564080714&rft_doaj_id=oai_doaj_org_article_b4064dfc3c44436fac97cee19e6c228a&rfr_iscdi=true |