Unique human immune signature of Ebola virus disease in Guinea
Research paper by
Paula Ruibal, Lisa Oestereich, Anja Lüdtke, Beate Becker-Ziaja, David M. Wozniak, Romy Kerber, Miša Korva, Mar Cabeza-Cabrerizo, Joseph A. Bore, Fara Raymond Koundouno, Sophie Duraffour, Romy Weller, Anja Thorenz, Eleonora Cimini, Domenico Viola, Chiara Agrati, Johanna Repits, Babak Afrough, Lauren A. Cowley, Didier Ngabo, Julia Hinzmann, Marc Mertens, Inês Vitoriano, Christopher H. Logue, Jan Peter Boettcher, Elisa Pallasch, Andreas Sachse, Amadou Bah, Katja Nitzsche, Eeva Kuisma, Janine Michel, Tobias Holm, Elsa-Gayle Zekeng, Isabel García-Dorival, Roman Wölfel, Kilian Stoecker, Erna Fleischmann, Thomas Strecker, Antonino Di Caro, Tatjana Avšič-Županc, Andreas Kurth, Silvia Meschi, Stephane Mély, Edmund Newman, Anne Bocquin, Zoltan Kis, Anne Kelterbaum, Peter Molkenthin, Fabrizio Carletti, Jasmine Portmann, Svenja Wolff, Concetta Castilletti, Gordian Schudt, Alexandra Fizet, Lisa J. Ottowell, Eva Herker, Thomas Jacobs, Birte Kretschmer, Ettore Severi, Nobila Ouedraogo, Mar Lago, A...
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 EVD1. In particular, very little is known about human immune responses to Ebola virus2, 3. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center 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 identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4+ and CD8+ T cells expressing the inhibitory molecules CTLA-4 and PD-1, which 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. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.