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DOI 10.1038/nature17949

Медицинская библиотека · Nature · 2016

Unique human immune signature of Ebola virus disease in Guinea.

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

СтатьяПоддержка NIH: внешняя программаResearch Support, N.I.H., IntramuralПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

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.

Для цитирования: 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. Unique human immune signature of Ebola virus disease in Guinea.. Nature. 2016. DOI: 10.1038/nature17949.

Предметные рубрики MeSH

CTLA-4 AntigenEbolavirusFemaleFlow CytometryGuineaHemorrhagic Fever, EbolaHumansInflammation MediatorsLongitudinal StudiesLymphocyte ActivationMalePatient DischargeProgrammed Cell Death 1 ReceptorSurvivorsT-LymphocytesViral Load
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