201. Unique human immune signature of Ebola virus disease in Guinea
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Isabel García-Dorival, Thomas Jacobs, Eleonora Cimini, Babak Afrough, Silvia Meschi, Marylyn M. Addo, Eeva Kuisma, Sophie Duraffour, Mar Lago, Mary Carrington, Paula Ruibal, Martin Gabriel, Erna Fleischmann, Beate Becker-Ziaja, Michel Van Herp, César Muñoz-Fontela, Nobila Ouedraogo, Peter Molkenthin, Sylvie Jonckheere, Didier Ngabo, Anne Kelterbaum, Andreas Kurth, Anja Thorenz, Pedro Anda, Lamine Koivogui, Tatjana Avšič-Županc, Stefan Schmiedel, Fara Raymond Koundouno, David M. Wozniak, Janine Michel, Zoltán Kis, Katja Nitzsche, Mar Cabeza-Cabrerizo, Benno Kreuels, Tobias Holm, Christopher H. Logue, Eva Herker, Stéphane Mély, Anne Bocquin, Julia Hinzmann, Fabrizio Carletti, N’Faly Magassouba, Patrick Drury, Antonino Di Caro, Leticia Franco, Jan Peter Boettcher, Anja Lüdtke, Joseph Akoi Bore, Romy Weller, Gao Xiaojiang, Dominic Wichmann, Inês Vitoriano, Alexandra Fizet, Carlos M. Castro, Kilian Stoecker, Lisa Oestereich, Osvaldo Miranda, Marc Mertens, Jasmine Portmann, Hilde De Clerck, Ansgar W. Lohse, Lisa J. Ottowell, Andreas Sachse, Stephan Günther, Chiara Agrati, Concetta Castilletti, Roman Wölfel, Carolina Nanclares, Armand Sprecher, Thomas Strecker, Johanna Repits, Elisa Pallasch, Boubacar Diallo, Birte Kretschmer, Miša Korva, Lauren A. Cowley, Anabel Negredo, Elsa-Gayle Zekeng, Ettore Severi, Miles W. Carroll, Amadou Bah, Domenico Viola, Pierre Formenty, Romy Kerber, Svenja Wolff, Edmund N. C. Newman, Gordian Schudt, and TWINCORE, Centre for experimental and clinical infection research GmbH, Feodor-Lynen Str. 7, 30625 Hannover, Germany.
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0301 basic medicine ,Male ,T cell ,viruses ,T-Lymphocytes ,Programmed Cell Death 1 Receptor ,Disease ,medicine.disease_cause ,Lymphocyte Activation ,Virus ,Article ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Humans ,CTLA-4 Antigen ,Longitudinal Studies ,Survivors ,Ebolavirus ,Multidisciplinary ,Ebola virus ,business.industry ,Hemorrhagic Fever, Ebola ,Viral Load ,Flow Cytometry ,Virology ,Patient Discharge ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,Immunology ,Female ,Guinea ,Inflammation Mediators ,business ,Viral load ,CD8 ,030215 immunology - Abstract
Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD 1 . In particular, very little is known about human immune responses to Ebola virus (EBOV) 2,3 . Here, we have for the first time evaluated the physiology of the human T cell immune response in EVD patients at the time of admission at the Ebola Treatment Center (ETC) in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we have identified an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by high percentage of CD4 and CD8 T cells expressing the inhibitory molecules cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1), which was correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation despite comparable overall T cell activation. Concommittant with virus clearance, survivors mounted a robust EBOV-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.
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