Different features of Vδ2 T and NK cells in fatal and non-fatal human Ebola infections

被引：37

作者：

Cimini, Eleonora ^{[1
]}

Viola, Domenico ^{[1
]}

Cabeza-Cabrerizo, Mar ^{[2
,3
]}

Romanelli, Antonella ^{[1
]}

Tumino, Nicola ^{[1
]}

Sacchi, Alessandra ^{[1
]}

Bordoni, Veronica ^{[1
]}

Casetti, Rita ^{[1
]}

Turchi, Federica ^{[1
]}

Martini, Federico ^{[1
]}

Bore, Joseph A. ^{[2
]}

Koundouno, Fara Raymond ^{[2
]}

Duraffour, Sophie ^{[2
,3
]}

Michel, Janine ^{[2
,4
]}

Holm, Tobias ^{[2
,3
]}

Zekeng, Elsa Gayle ^{[2
,5
]}

Cowley, Lauren ^{[2
,6
,7
]}

Dorival, Isabel Garcia ^{[2
,5
]}

Doerrbecker, Juliane ^{[2
,3
,8
]}

Hetzelt, Nicole ^{[2
,4
]}

Baum, Jonathan H. J. ^{[2
,3
,9
]}

Portmann, Jasmine ^{[2
]}

Woelfel, Roman ^{[2
,10
,11
]}

Gabriel, Martin ^{[2
,3
,11
]}

Miranda, Osvaldo ^{[12
]}

Diaz, Graciliano ^{[12
]}

Diaz, Jose E. ^{[12
]}

Fleites, Yoel A. ^{[12
]}

Pineiro, Carlos A. ^{[12
]}

Castro, Carlos M. ^{[12
]}

Koivogui, Lamine ^{[13
]}

Magassouba, N'Faly ^{[14
]}

Diallo, Boubacar ^{[15
,16
]}

Ruibal, Paula ^{[2
,3
,17
]}

Oestereich, Lisa ^{[2
,3
,11
]}

Wozniak, David M. ^{[2
,3
,11
]}

Luedtke, Anja ^{[2
,3
,11
,17
]}

Becker-Ziaja, Beate ^{[2
,3
,11
]}

Capobianchi, Maria R. ^{[1
]}

Ippolito, Giuseppe ^{[1
]}

Carroll, Miles W. ^{[2
,18
]}

Guenther, Stephan ^{[2
,3
,11
]}

Di Caro, Antonino ^{[1
,2
]}

Munoz-Fontela, Cesar ^{[2
,3
,11
,17
]}

Agrati, Chiara ^{[1
]}

机构：

[1] Natl Inst Infect Dis Lazzaro Spallanzani, Dept Epidemiol & Preclin Res, Rome, Italy

[2] European Mobile Lab Consortium, Hamburg, Germany

[3] WHO, Collaborating Ctr Arbovirus & Hemorrhag Fever Ref, Dept Virol, Bernhard Nocht Inst Trop Med, Hamburg, Germany

[4] Robert Koch Inst, Berlin, Germany

[5] Univ Liverpool, Inst Infect & Global Hlth, Liverpool, Merseyside, England

[6] Publ Hlth England, Natl Infect Serv, Porton Down, England

[7] Publ Hlth England, Natl Infect Serv, Colindale, England

[8] Inst Expt Virol, Ctr Expt & Clin Infect Res TWINCORE, Hannover, Germany

[9] Fed Off Civil Protect, Spiez Lab, Bern, Switzerland

[10] Bundeswehr Inst Microbiol, Munich, Germany

[11] German Ctr Infect Res DZIF, Partner Sites Hamburg, Munich, Germany

[12] Hosp Militar Cent Dr Carlos J Finlay, Havana, Cuba

[13] Inst Natl Sante Publ, Conakry, Guinea

[14] Univ Gamal Abdel Nasser Conakry, Lab Fievres Hemorrag Guinee, Conakry, Guinea

[15] WHO, Geneva, Switzerland

[16] WHO, Conakry, Switzerland

[17] Leibniz Inst Expt Virol, Heinrich Pette Inst, Hamburg, Germany

[18] Univ Southampton, South Gen Hosp, Southampton, Hants, England

来源：

PLOS NEGLECTED TROPICAL DISEASES | 2017年 / 11卷 / 05期

关键词：

NATURAL-KILLER-CELLS; HEMORRHAGIC-FEVER; INNATE PROTECTION; DENDRITIC CELLS; VIRUS INFECTION; ACTIVATION; DEATH; PATHOGENESIS; MACROPHAGES; MACAQUES;

D O I：

10.1371/journal.pntd.0005645

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Background Human Ebola infection is characterized by a paralysis of the immune system. A signature of alpha beta T cells in fatal Ebola infection has been recently proposed, while the involvement of innate immune cells in the protection/pathogenesis of Ebola infection is unknown. Aim of this study was to analyze gamma delta T and NK cells in patients from the Ebola outbreak of 2014-2015 occurred in West Africa, and to assess their association with the clinical outcome. Methodology/Principal findings Nineteen Ebola-infected patients were enrolled at the time of admission to the Ebola Treatment Centre in Guinea. Patients were divided in two groups on the basis of the clinical outcome. The analysis was performed by using multiparametric flow cytometry established by the European Mobile Laboratory in the field. A low frequency of V delta 2 T-cells was observed during Ebola infection, independently from the clinical outcome. Moreover, V delta 2 T-cells from Ebola patients massively expressed CD95 apoptotic marker, suggesting the involvement of apoptotic mechanisms in V delta 2 T-cell loss. Interestingly, V delta 2 T-cells from survivors expressed an effector phenotype and presented a lower expression of the CTLA-4 exhaustion marker than fatalities, suggesting a role of effector V delta 2 T-cells in the protection. Furthermore, patients with fatal Ebola infection were characterized by a lower NK cell frequency than patients with non fatal infection. In particular, both CD56(bright) and CD56(dim) NK frequency were very low both in fatal and non fatal infections, while a higher frequency of CD56(neg) NK cells was associated to non-fatal infections. Finally, NK activation and expression of NKp46 and CD158a were independent from clinical outcome. Conclusions/Significances Altogether, the data suggest that both effector V delta 2 T-cells and NK cells may play a role in the complex network of protective response to EBOV infection. Further studies are required to characterize the protective effector functions of V delta 2 and NK cells.

引用

页数：11

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