Unique human immune signature of Ebola virus disease in Guinea

TY - JOUR

T1 - Unique human immune signature of Ebola virus disease in Guinea

AU - Ruibal, Paula

AU - Oestereich, Lisa

AU - Lüdtke, Anja

AU - Becker-Ziaja, Beate

AU - Wozniak, David M

AU - Kerber, Romy

AU - Korva, Miša

AU - Cabeza-Cabrerizo, Mar

AU - Bore, Joseph A

AU - Koundouno, Fara Raymond

AU - Duraffour, Sophie

AU - Weller, Romy

AU - Thorenz, Anja

AU - Cimini, Eleonora

AU - Viola, Domenico

AU - Agrati, Chiara

AU - Repits, Johanna

AU - Afrough, Babak

AU - Cowley, Lauren A

AU - Ngabo, Didier

AU - Hinzmann, Julia

AU - Mertens, Marc

AU - Vitoriano, Inês

AU - Logue, Christopher H

AU - Boettcher, Jan Peter

AU - Pallasch, Elisa

AU - Sachse, Andreas

AU - Bah, Amadou

AU - Nitzsche, Katja

AU - Kuisma, Eeva

AU - Michel, Janine

AU - Holm, Tobias

AU - Zekeng, Elsa-Gayle

AU - García-Dorival, Isabel

AU - Wölfel, Roman

AU - Stoecker, Kilian

AU - Fleischmann, Erna

AU - Strecker, Thomas

AU - Di Caro, Antonino

AU - Avšič-Županc, Tatjana

AU - Kurth, Andreas

AU - Meschi, Silvia

AU - Mély, Stephane

AU - Newman, Edmund

AU - Bocquin, Anne

AU - Kis, Zoltan

AU - Kelterbaum, Anne

AU - Molkenthin, Peter

AU - Carletti, Fabrizio

AU - Portmann, Jasmine

AU - Wolff, Svenja

AU - Castilletti, Concetta

AU - Schudt, Gordian

AU - Fizet, Alexandra

AU - Ottowell, Lisa J

AU - Herker, Eva

AU - Jacobs, Thomas

AU - Kretschmer, Birte

AU - Severi, Ettore

AU - Ouedraogo, Nobila

AU - Lago, Mar

AU - Negredo, Anabel

AU - Franco, Leticia

AU - Anda, Pedro

AU - Schmiedel, Stefan

AU - Kreuels, Benno

AU - Wichmann, Dominic

AU - Addo, Marylyn M

AU - Lohse, Ansgar W

AU - De Clerck, Hilde

AU - Nanclares, Carolina

AU - Jonckheere, Sylvie

AU - Van Herp, Michel

AU - Sprecher, Armand

AU - Xiaojiang, Gao

AU - Carrington, Mary

AU - Miranda, Osvaldo

AU - Castro, Carlos M

AU - Gabriel, Martin

AU - Drury, Patrick

AU - Formenty, Pierre

AU - Diallo, Boubacar

AU - Koivogui, Lamine

AU - Magassouba, N'Faly

AU - Carroll, Miles W

AU - Günther, Stephan

AU - Muñoz-Fontela, César

PY - 2016/5/5

Y1 - 2016/5/5

N2 - 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.

AB - 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.

KW - CTLA-4 Antigen

KW - Ebolavirus

KW - Female

KW - Flow Cytometry

KW - Guinea

KW - Hemorrhagic Fever, Ebola

KW - Humans

KW - Inflammation Mediators

KW - Longitudinal Studies

KW - Lymphocyte Activation

KW - Male

KW - Patient Discharge

KW - Programmed Cell Death 1 Receptor

KW - Survivors

KW - T-Lymphocytes

KW - Viral Load

U2 - 10.1038/nature17949

DO - 10.1038/nature17949

M3 - SCORING: Journal article

C2 - 27147028

VL - 533

SP - 100

EP - 104

JO - NATURE

JF - NATURE

SN - 0028-0836

IS - 7601

ER -