Unique Human Immune Signature of Ebola Virus Disease in Guinea

Hdl Handle:
http://hdl.handle.net/10144/612892
Title:
Unique Human Immune Signature of Ebola Virus Disease in Guinea
Authors:
Ruibal, P; Oestereich, L; Lüdtke, A; Becker-Ziaja, B; Wozniak, DM; Kerber, R; Korva, M; Cabeza-Cabrerizo, M; Bore, JA; Koundouno, FR; Duraffour, S; Weller, R; Thorenz, A; Cimini, E; Viola, D; Agrati, C; Repits, J; Afrough, B; Cowley, LA; Ngabo, D; Hinzmann, J; Mertens, M; Vitoriano, I; Logue, CH; Boettcher, JP; Pallasch, E; Sachse, A; Bah, A; Nitzsche, K; Kuisma, E; Michel, J; Holm, T; Zekeng, EG; García-Dorival, I; Wölfel, R; Stoecker, K; Fleischmann, E; Strecker, T; Di Caro, A; Avšič-Županc, T; Kurth, A; Meschi, S; Mély, S; Newman, E; Bocquin, A; Kis, Z; Kelterbaum, A; Molkenthin, P; Carletti, F; Portmann, J; Wolff, S; Castilletti, C; Schudt, G; Fizet, A; Ottowell, LJ; Herker, E; Jacobs, T; Kretschmer, B; Severi, E; Ouedraogo, N; Lago, M; Negredo, A; Franco, L; Anda, P; Schmiedel, S; Kreuels, B; Wichmann, D; Addo, MM; Lohse, AW; De Clerck, H; Nanclares, C; Jonckheere, S; Van Herp, M; Sprecher, A; Xiaojiang, G; Carrington, M; Miranda, O; Castro, CM; Gabriel, M; Drury, P; Formenty, P; Diallo, B; Koivogui, L; Magassouba, N; Carroll, MW; Günther, S; Muñoz-Fontela, C
Journal:
Nature
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.
Publisher:
Nature Publishing Group
Issue Date:
5-May-2016
URI:
http://hdl.handle.net/10144/612892
DOI:
10.1038/nature17949
PubMed ID:
27147028
Language:
en
ISSN:
1476-4687
Appears in Collections:
Other Diseases

Full metadata record

DC FieldValue Language
dc.contributor.authorRuibal, Pen
dc.contributor.authorOestereich, Len
dc.contributor.authorLüdtke, Aen
dc.contributor.authorBecker-Ziaja, Ben
dc.contributor.authorWozniak, DMen
dc.contributor.authorKerber, Ren
dc.contributor.authorKorva, Men
dc.contributor.authorCabeza-Cabrerizo, Men
dc.contributor.authorBore, JAen
dc.contributor.authorKoundouno, FRen
dc.contributor.authorDuraffour, Sen
dc.contributor.authorWeller, Ren
dc.contributor.authorThorenz, Aen
dc.contributor.authorCimini, Een
dc.contributor.authorViola, Den
dc.contributor.authorAgrati, Cen
dc.contributor.authorRepits, Jen
dc.contributor.authorAfrough, Ben
dc.contributor.authorCowley, LAen
dc.contributor.authorNgabo, Den
dc.contributor.authorHinzmann, Jen
dc.contributor.authorMertens, Men
dc.contributor.authorVitoriano, Ien
dc.contributor.authorLogue, CHen
dc.contributor.authorBoettcher, JPen
dc.contributor.authorPallasch, Een
dc.contributor.authorSachse, Aen
dc.contributor.authorBah, Aen
dc.contributor.authorNitzsche, Ken
dc.contributor.authorKuisma, Een
dc.contributor.authorMichel, Jen
dc.contributor.authorHolm, Ten
dc.contributor.authorZekeng, EGen
dc.contributor.authorGarcía-Dorival, Ien
dc.contributor.authorWölfel, Ren
dc.contributor.authorStoecker, Ken
dc.contributor.authorFleischmann, Een
dc.contributor.authorStrecker, Ten
dc.contributor.authorDi Caro, Aen
dc.contributor.authorAvšič-Županc, Ten
dc.contributor.authorKurth, Aen
dc.contributor.authorMeschi, Sen
dc.contributor.authorMély, Sen
dc.contributor.authorNewman, Een
dc.contributor.authorBocquin, Aen
dc.contributor.authorKis, Zen
dc.contributor.authorKelterbaum, Aen
dc.contributor.authorMolkenthin, Pen
dc.contributor.authorCarletti, Fen
dc.contributor.authorPortmann, Jen
dc.contributor.authorWolff, Sen
dc.contributor.authorCastilletti, Cen
dc.contributor.authorSchudt, Gen
dc.contributor.authorFizet, Aen
dc.contributor.authorOttowell, LJen
dc.contributor.authorHerker, Een
dc.contributor.authorJacobs, Ten
dc.contributor.authorKretschmer, Ben
dc.contributor.authorSeveri, Een
dc.contributor.authorOuedraogo, Nen
dc.contributor.authorLago, Men
dc.contributor.authorNegredo, Aen
dc.contributor.authorFranco, Len
dc.contributor.authorAnda, Pen
dc.contributor.authorSchmiedel, Sen
dc.contributor.authorKreuels, Ben
dc.contributor.authorWichmann, Den
dc.contributor.authorAddo, MMen
dc.contributor.authorLohse, AWen
dc.contributor.authorDe Clerck, Hen
dc.contributor.authorNanclares, Cen
dc.contributor.authorJonckheere, Sen
dc.contributor.authorVan Herp, Men
dc.contributor.authorSprecher, Aen
dc.contributor.authorXiaojiang, Gen
dc.contributor.authorCarrington, Men
dc.contributor.authorMiranda, Oen
dc.contributor.authorCastro, CMen
dc.contributor.authorGabriel, Men
dc.contributor.authorDrury, Pen
dc.contributor.authorFormenty, Pen
dc.contributor.authorDiallo, Ben
dc.contributor.authorKoivogui, Len
dc.contributor.authorMagassouba, Nen
dc.contributor.authorCarroll, MWen
dc.contributor.authorGünther, Sen
dc.contributor.authorMuñoz-Fontela, Cen
dc.date.accessioned2016-06-13T19:33:58Zen
dc.date.available2016-06-13T19:33:58Zen
dc.date.issued2016-05-05en
dc.identifier.citationUnique human immune signature of Ebola virus disease in Guinea. 2016, 533 (7601):100-4 Natureen
dc.identifier.issn1476-4687en
dc.identifier.pmid27147028en
dc.identifier.doi10.1038/nature17949en
dc.identifier.urihttp://hdl.handle.net/10144/612892en
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.language.isoenen
dc.publisherNature Publishing Groupen
dc.rightsArchived on this site with permission from Macmillan Publishers Ltd. Copyright 200Xen
dc.titleUnique Human Immune Signature of Ebola Virus Disease in Guineaen
dc.identifier.journalNatureen

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