2.50
Hdl Handle:
http://hdl.handle.net/10033/620583
Title:
Unique human immune signature of Ebola virus disease in Guinea.
Authors:
Ruibal, Paula; Oestereich, Lisa; Lüdtke, Anja; Becker-Ziaja, Beate; Wozniak, David M; Kerber, Romy; Korva, Miša; Cabeza-Cabrerizo, Mar; Bore, Joseph A; Koundouno, Fara Raymond; Duraffour, Sophie; Weller, Romy; Thorenz, Anja; Cimini, Eleonora; Viola, Domenico; Agrati, Chiara; Repits, Johanna; Afrough, Babak; Cowley, Lauren A; Ngabo, Didier; Hinzmann, Julia; Mertens, Marc; Vitoriano, Inês; Logue, Christopher H; Boettcher, Jan Peter; Pallasch, Elisa; Sachse, Andreas; Bah, Amadou; Nitzsche, Katja; Kuisma, Eeva; Michel, Janine; Holm, Tobias; Zekeng, Elsa-Gayle; García-Dorival, Isabel; Wölfel, Roman; Stoecker, Kilian; Fleischmann, Erna; Strecker, Thomas; Di Caro, Antonino; Avšič-Županc, Tatjana; Kurth, Andreas; Meschi, Silvia; Mély, Stephane; Newman, Edmund; Bocquin, Anne; Kis, Zoltan; Kelterbaum, Anne; Molkenthin, Peter; Carletti, Fabrizio; Portmann, Jasmine; Wolff, Svenja; Castilletti, Concetta; Schudt, Gordian; Fizet, Alexandra; Ottowell, Lisa J; Herker, Eva; Jacobs, Thomas; Kretschmer, Birte; Severi, Ettore; Ouedraogo, Nobila; Lago, Mar; Negredo, Anabel; Franco, Leticia; Anda, Pedro; Schmiedel, Stefan; Kreuels, Benno; Wichmann, Dominic; Addo, Marylyn M; Lohse, Ansgar W; De Clerck, Hilde; Nanclares, Carolina; Jonckheere, Sylvie; Van Herp, Michel; Sprecher, Armand; Xiaojiang, Gao; Carrington, Mary; Miranda, Osvaldo; Castro, Carlos M; Gabriel, Martin; Drury, Patrick; Formenty, Pierre; Diallo, Boubacar; Koivogui, Lamine; Magassouba, N'Faly; Carroll, Miles W; Günther, Stephan; Muñoz-Fontela, César
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.
Affiliation:
TWINCORE, Centre for experimental and clinical infection research GmbH, Feodor-Lynen Str. 7, 30625 Hannover, Germany.
Citation:
Unique human immune signature of Ebola virus disease in Guinea. 2016, 533 (7601):100-4 Nature
Journal:
Nature
Issue Date:
5-May-2016
URI:
http://hdl.handle.net/10033/620583
DOI:
10.1038/nature17949
PubMed ID:
27147028
Type:
Article
ISSN:
0028-0836
Appears in Collections:
publications of the department experimental Virology([TC]EVIR)

Full metadata record

DC FieldValue Language
dc.contributor.authorRuibal, Paulaen
dc.contributor.authorOestereich, Lisaen
dc.contributor.authorLüdtke, Anjaen
dc.contributor.authorBecker-Ziaja, Beateen
dc.contributor.authorWozniak, David Men
dc.contributor.authorKerber, Romyen
dc.contributor.authorKorva, Mišaen
dc.contributor.authorCabeza-Cabrerizo, Maren
dc.contributor.authorBore, Joseph Aen
dc.contributor.authorKoundouno, Fara Raymonden
dc.contributor.authorDuraffour, Sophieen
dc.contributor.authorWeller, Romyen
dc.contributor.authorThorenz, Anjaen
dc.contributor.authorCimini, Eleonoraen
dc.contributor.authorViola, Domenicoen
dc.contributor.authorAgrati, Chiaraen
dc.contributor.authorRepits, Johannaen
dc.contributor.authorAfrough, Babaken
dc.contributor.authorCowley, Lauren Aen
dc.contributor.authorNgabo, Didieren
dc.contributor.authorHinzmann, Juliaen
dc.contributor.authorMertens, Marcen
dc.contributor.authorVitoriano, Inêsen
dc.contributor.authorLogue, Christopher Hen
dc.contributor.authorBoettcher, Jan Peteren
dc.contributor.authorPallasch, Elisaen
dc.contributor.authorSachse, Andreasen
dc.contributor.authorBah, Amadouen
dc.contributor.authorNitzsche, Katjaen
dc.contributor.authorKuisma, Eevaen
dc.contributor.authorMichel, Janineen
dc.contributor.authorHolm, Tobiasen
dc.contributor.authorZekeng, Elsa-Gayleen
dc.contributor.authorGarcía-Dorival, Isabelen
dc.contributor.authorWölfel, Romanen
dc.contributor.authorStoecker, Kilianen
dc.contributor.authorFleischmann, Ernaen
dc.contributor.authorStrecker, Thomasen
dc.contributor.authorDi Caro, Antoninoen
dc.contributor.authorAvšič-Županc, Tatjanaen
dc.contributor.authorKurth, Andreasen
dc.contributor.authorMeschi, Silviaen
dc.contributor.authorMély, Stephaneen
dc.contributor.authorNewman, Edmunden
dc.contributor.authorBocquin, Anneen
dc.contributor.authorKis, Zoltanen
dc.contributor.authorKelterbaum, Anneen
dc.contributor.authorMolkenthin, Peteren
dc.contributor.authorCarletti, Fabrizioen
dc.contributor.authorPortmann, Jasmineen
dc.contributor.authorWolff, Svenjaen
dc.contributor.authorCastilletti, Concettaen
dc.contributor.authorSchudt, Gordianen
dc.contributor.authorFizet, Alexandraen
dc.contributor.authorOttowell, Lisa Jen
dc.contributor.authorHerker, Evaen
dc.contributor.authorJacobs, Thomasen
dc.contributor.authorKretschmer, Birteen
dc.contributor.authorSeveri, Ettoreen
dc.contributor.authorOuedraogo, Nobilaen
dc.contributor.authorLago, Maren
dc.contributor.authorNegredo, Anabelen
dc.contributor.authorFranco, Leticiaen
dc.contributor.authorAnda, Pedroen
dc.contributor.authorSchmiedel, Stefanen
dc.contributor.authorKreuels, Bennoen
dc.contributor.authorWichmann, Dominicen
dc.contributor.authorAddo, Marylyn Men
dc.contributor.authorLohse, Ansgar Wen
dc.contributor.authorDe Clerck, Hildeen
dc.contributor.authorNanclares, Carolinaen
dc.contributor.authorJonckheere, Sylvieen
dc.contributor.authorVan Herp, Michelen
dc.contributor.authorSprecher, Armanden
dc.contributor.authorXiaojiang, Gaoen
dc.contributor.authorCarrington, Maryen
dc.contributor.authorMiranda, Osvaldoen
dc.contributor.authorCastro, Carlos Men
dc.contributor.authorGabriel, Martinen
dc.contributor.authorDrury, Patricken
dc.contributor.authorFormenty, Pierreen
dc.contributor.authorDiallo, Boubacaren
dc.contributor.authorKoivogui, Lamineen
dc.contributor.authorMagassouba, N'Falyen
dc.contributor.authorCarroll, Miles Wen
dc.contributor.authorGünther, Stephanen
dc.contributor.authorMuñoz-Fontela, Césaren
dc.date.accessioned2016-11-17T12:19:23Z-
dc.date.available2016-11-17T12:19:23Z-
dc.date.issued2016-05-05-
dc.identifier.citationUnique human immune signature of Ebola virus disease in Guinea. 2016, 533 (7601):100-4 Natureen
dc.identifier.issn0028-0836-
dc.identifier.pmid27147028-
dc.identifier.doi10.1038/nature17949-
dc.identifier.urihttp://hdl.handle.net/10033/620583-
dc.description.abstractDespite 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.en
dc.languageENG-
dc.relation: info:eu-repo/grantAgreement/H2020/666100en
dc.rightsopenAccessen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshCTLA-4 Antigenen
dc.subject.meshEbolavirusen
dc.subject.meshFemaleen
dc.subject.meshFlow Cytometryen
dc.subject.meshGuineaen
dc.subject.meshHemorrhagic Fever, Ebolaen
dc.subject.meshHumansen
dc.subject.meshInflammation Mediatorsen
dc.subject.meshLongitudinal Studiesen
dc.subject.meshLymphocyte Activationen
dc.subject.meshMaleen
dc.subject.meshPatient Dischargeen
dc.subject.meshProgrammed Cell Death 1 Receptoren
dc.subject.meshSurvivorsen
dc.subject.meshT-Lymphocytesen
dc.subject.meshViral Loaden
dc.titleUnique human immune signature of Ebola virus disease in Guinea.
dc.typeArticleen
dc.contributor.departmentTWINCORE, Centre for experimental and clinical infection research GmbH, Feodor-Lynen Str. 7, 30625 Hannover, Germany.en
dc.identifier.journalNatureen

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