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

Eleonora Cimini, Domenico Viola, Mar Cabeza-Cabrerizo, Antonella Romanelli, Nicola Tumino, Alessandra Sacchi, Veronica Bordoni, Rita Casetti, Federica Turchi, Federico Martini, Joseph Bore, Fara Raymond Koundouno, Sophie Duraffour, Janine Michel, Tobias Holm, Elsa Zekeng, Lauren Cowley, Isabel Garcia-Dorival, Juliane Doerrbecker, Nicole HetzeltJonathan Baum, Jasmine Portmann, Roman Wölfel, Martin Gabriel, Osvaldo Miranda, Graciliano Diaz, Jose Diaz, Yoel Fleites, Carlos Piñeiro, Carlos Castro, Lamine Koivogui, N'Faly Magassouba, Boubacar Diallo, Paula Ruibal, Lisa Oestereich, David Wozniak, Anja Lüdtke, Beate Becker-Ziaja, Maria Capobianchi, Giuseppe Ippolito, Miles Carroll, Stephan Günther, Antonino Di Caro, Cesar Muñoz-Fontela, Chiara Agrati

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Abstract

Background
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.

Author summary
Human Ebola infection presents a high lethality rate and is characterized by a paralysis of the immune response. The definition of the protective immune profile during Ebola infection represents a main challenge useful in vaccine and therapy design.

In particular, the protective/pathogenetic involvement of innate immune cells during Ebola infection in humans remains to be clarified. Nineteen Ebola-infected patients were enrolled at the time of admission to the Ebola Treatment Center in Guinea, and the profiling of innate immunity was correlated with the clinical outcome. Our results show that both effector Vδ2 T-cells and NK cells were associated with survival, suggesting their involvement in the complex network of protective response to EBOV infection.
Original languageEnglish
Article numbere0005645
JournalPLoS Neglected Tropical Diseases
Volume11
Issue number5
DOIs
Publication statusPublished - 30 May 2017

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