Unique human immune signature of Ebola virus disease in Guinea

Paula Ruibal, Lisa Oestereich, Anja Ludtke, 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 NgaboJulia 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 Garcia-Dorival, Roman Wolfel, Kilian Stoecker, Erna Fleischmann, Thomas Strecker, Antonino Di Caro, Tatjana Avsic-Zupanc, Andreas Kurth, Silvia Meschi, Stephane Mely, 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, Anabel Negredo, Leticia Franco, Pedro Anda, Stefan Schmiedel, Benno Kreuels, Dominic Wichmann, Marylyn M. Addo, Ansgar W. Lohse, Hilde De Clerck, Carolina Nanclares, Sylvie Jonckheere, Michel Van Herp, Armand Sprecher, Gao Xiaojiang, Mary Carrington, Osvaldo Miranda, Carlos M. Castro, Martin Gabriel, Patrick Drury, Pierre Formenty, Boubacar Diallo, Lamine Koivogui, N'Faly Magassouba, Miles W. Carroll, Stephan Gunther, Cesar Munoz-Fontela

Research output: Contribution to journalArticlepeer-review

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. In particular, very little is known about human immune responses to Ebola virus. 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.

Original languageEnglish
Pages (from-to)100-104
Number of pages5
JournalNature
Volume533
Issue number7601
DOIs
Publication statusPublished - May 4 2016

ASJC Scopus subject areas

  • Medicine(all)
  • General

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