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Nature. 2016 May 5;533(7601):100-4. doi: 10.1038/nature17949.

Unique human immune signature of Ebola virus disease in Guinea.

Author information

1
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
2
Bernhard Nocht Institute for Tropical Medicine, World Health Organization Collaborating Center for Arbovirus and Hemorrhagic Fever Reference and Research, 20359 Hamburg, Germany.
3
German Center for Infection Research (DZIF), Partner Sites Hamburg, Munich, and Marburg, Germany.
4
European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany.
5
Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
6
Institute of Experimental Virology, Twincore, Center for Experimental and Clinical Infection Research, 30625 Hannover, Germany.
7
Hannover Medical School, 30625 Hannover, Germany.
8
National Institute for Infectious Diseases 'Lazzaro Spallanzani', 00149 Rome, Italy.
9
Public Health England, Porton Down, Salisbury SP4 0JG, UK.
10
Public Health England, Colindale Ave, London NW9 5EQ, UK.
11
Robert Koch Institute, 13353 Berlin, Germany.
12
Friedrich Loeffler Institute, 17493 Greifswald-Island of Riems, Germany.
13
Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland.
14
Institute of Infection and Global Health, University of Liverpool, Liverpool L69 7BE, UK.
15
Bundeswehr Institute of Microbiology, 80937 Munich, Germany.
16
Institute of Virology, Philipps University, 35043 Marburg, Germany.
17
Laboratoire P4-Jean Mérieux, US003 INSERM, 69365 Lyon, France.
18
National Center for Epidemiology, Hungarian National Biosafety Laboratory, H1097 Budapest, Hungary.
19
European Centre for Disease Prevention and Control, 171 65 Solna, Sweden.
20
Federal Office for Civil Protection, CH-3700 Spiez, Switzerland.
21
Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, 69365 Lyon, France.
22
Eurice, European Research and Project Office, 10115 Berlin, Germany.
23
Infectious Diseases Unit, Internal Medicine Service, Hospital La Paz, 28046 Madrid, Spain.
24
National Center of Microbiology, Institute of Health 'Carlos III', 28220 Madrid, Spain.
25
University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
26
Médecins sans Frontières, B-1050 Brussels, Belgium.
27
Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA.
28
Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139, USA.
29
Hospital Militar Central Dr. Carlos J. Finlay, 11400 Havana, Cuba.
30
World Health Organization, 1211 Geneva 27, Switzerland.
31
Institut National de Santé Publique, 2101 Conakry, Guinea.
32
Université Gamal Abdel Nasser de Conakry, CHU Donka, 2101 Conakry, Guinea.

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.

PMID:
27147028
PMCID:
PMC4876960
DOI:
10.1038/nature17949
[Indexed for MEDLINE]
Free PMC Article

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