Cimini Eleonora, Viola Domenico, Cabeza-Cabrerizo Mar, Romanelli Antonella, Tumino Nicola, Sacchi Alessandra, Bordoni Veronica, Casetti Rita, Turchi Federica, Martini Federico, Bore Joseph A, Koundouno Fara Raymond, Duraffour Sophie, Michel Janine, Holm Tobias, Zekeng Elsa Gayle, Cowley Lauren, Garcia Dorival Isabel, Doerrbecker Juliane, Hetzelt Nicole, Baum Jonathan H J, Portmann Jasmine, Wölfel Roman, Gabriel Martin, Miranda Osvaldo, Díaz Graciliano, Díaz José E, Fleites Yoel A, Piñeiro Carlos A, Castro Carlos M, Koivogui Lamine, Magassouba N'Faly, Diallo Boubacar, Ruibal Paula, Oestereich Lisa, Wozniak David M, Lüdtke Anja, Becker-Ziaja Beate, Capobianchi Maria R, Ippolito Giuseppe, Carroll Miles W, Günther Stephan, Di Caro Antonino, Muñoz-Fontela César, Agrati Chiara
Department of Epidemiology and Pre-clinical research, National Institute for Infectious Diseases "Lazzaro Spallanzani", Rome, Italy.
European Mobile Laboratory Consortium, Hamburg, Germany.
PLoS Negl Trop Dis. 2017 May 30;11(5):e0005645. doi: 10.1371/journal.pntd.0005645. eCollection 2017 May.
Human Ebola infection is characterized by a paralysis of the immune system. A signature of αβ 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 γδ 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 Vδ2 T-cells was observed during Ebola infection, independently from the clinical outcome. Moreover, Vδ2 T-cells from Ebola patients massively expressed CD95 apoptotic marker, suggesting the involvement of apoptotic mechanisms in Vδ2 T-cell loss. Interestingly, Vδ2 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 Vδ2 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 CD56bright and CD56dim NK frequency were very low both in fatal and non fatal infections, while a higher frequency of CD56neg 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 Vδ2 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 Vδ2 and NK cells.
人类埃博拉病毒感染的特征是免疫系统麻痹。最近有人提出了致命埃博拉病毒感染中αβ T细胞的特征，而固有免疫细胞在埃博拉病毒感染的保护/发病机制中的作用尚不清楚。本研究的目的是分析2014 - 2015年西非埃博拉疫情患者中的γδ T细胞和自然杀伤（NK）细胞，并评估它们与临床结局的关联。
方法/主要发现：19名埃博拉病毒感染患者在几内亚埃博拉治疗中心入院时被纳入研究。根据临床结局将患者分为两组。分析采用欧洲移动实验室在现场建立的多参数流式细胞术进行。在埃博拉病毒感染期间观察到Vδ2 T细胞频率较低，与临床结局无关。此外，埃博拉患者的Vδ2 T细胞大量表达CD95凋亡标志物，提示凋亡机制参与了Vδ2 T细胞的损失。有趣的是，幸存者的Vδ2 T细胞表现出效应器表型，并且与死亡患者相比，其细胞毒性T淋巴细胞相关抗原4（CTLA-4）耗竭标志物的表达较低，提示效应器Vδ2 T细胞在保护中发挥作用。此外，致命埃博拉病毒感染患者的特征是NK细胞频率低于非致命感染患者。特别是，在致命和非致命感染中，CD56bright和CD56dim NK细胞频率都非常低，而较高频率的CD56neg NK细胞与非致命感染相关。最后，NK细胞活化以及NKp46和CD158a的表达与临床结局无关。
结论/意义：总体而言，数据表明效应器Vδ2 T细胞和NK细胞可能在针对埃博拉病毒感染的复杂保护反应网络中发挥作用。需要进一步研究来表征Vδ2和NK细胞的保护效应功能。
