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 A. Bore, Fara Raymond Koundouno, Sophie Duraffour, Janine Michel, Tobias Holm, Elsa Gayle Zekeng, Lauren Cowley, Isabel Garcia Dorival, Juliane Doerrbecker, Nicole HetzeltJonathan H.J. Baum, Jasmine Portmann, Roman Wölfel, Martin Gabriel, Osvaldo Miranda, Graciliano Díaz, José E. Díaz, Yoel A. Fleites, Carlos A. Piñeiro, Carlos M. Castro, Lamine Koivogui, N’Faly Magassouba, Boubacar Diallo, Paula Ruibal, Lisa Oestereich, David M. Wozniak, Anja Lüdtke, Beate Becker-Ziaja, Maria R. Capobianchi, Giuseppe Ippolito, Miles W. Carroll, Stephan Günther, Antonino Di Caro, César Muñoz-Fontela, Chiara Agrati

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 CD56brightand CD56dimNK frequency were very low both in fatal and non fatal infections, while a higher frequency of CD56negNK 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.

Original languageEnglish
Article numbere0005645
JournalPLoS Neglected Tropical Diseases
Volume11
Issue number5
DOIs
Publication statusPublished - May 30 2017

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Ebola Hemorrhagic Fever
Natural Killer Cells
T-Lymphocytes
Cytoprotection
Infection
Guinea
Western Africa
Paralysis
Disease Outbreaks
Survivors
Immune System
Flow Cytometry

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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

In: PLoS Neglected Tropical Diseases, Vol. 11, No. 5, e0005645, 30.05.2017.

Research output: Contribution to journalArticle

Cimini, E, Viola, D, Cabeza-Cabrerizo, M, Romanelli, A, Tumino, N, Sacchi, A, Bordoni, V, Casetti, R, Turchi, F, Martini, F, Bore, JA, Koundouno, FR, Duraffour, S, Michel, J, Holm, T, Zekeng, EG, Cowley, L, Garcia Dorival, I, Doerrbecker, J, Hetzelt, N, Baum, JHJ, Portmann, J, Wölfel, R, Gabriel, M, Miranda, O, Díaz, G, Díaz, JE, Fleites, YA, Piñeiro, CA, Castro, CM, Koivogui, L, Magassouba, NF, Diallo, B, Ruibal, P, Oestereich, L, Wozniak, DM, Lüdtke, A, Becker-Ziaja, B, Capobianchi, MR, Ippolito, G, Carroll, MW, Günther, S, Di Caro, A, Muñoz-Fontela, C & Agrati, C 2017, 'Different features of Vδ2 T and NK cells in fatal and non-fatal human Ebola infections', PLoS Neglected Tropical Diseases, vol. 11, no. 5, e0005645. https://doi.org/10.1371/journal.pntd.0005645
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. / Different features of Vδ2 T and NK cells in fatal and non-fatal human Ebola infections. In: PLoS Neglected Tropical Diseases. 2017 ; Vol. 11, No. 5.
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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 CD56brightand CD56dimNK frequency were very low both in fatal and non fatal infections, while a higher frequency of CD56negNK 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.",
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T1 - Different features of Vδ2 T and NK cells in fatal and non-fatal human Ebola infections

AU - Cimini, Eleonora

AU - Viola, Domenico

AU - Cabeza-Cabrerizo, Mar

AU - Romanelli, Antonella

AU - Tumino, Nicola

AU - Sacchi, Alessandra

AU - Bordoni, Veronica

AU - Casetti, Rita

AU - Turchi, Federica

AU - Martini, Federico

AU - Bore, Joseph A.

AU - Koundouno, Fara Raymond

AU - Duraffour, Sophie

AU - Michel, Janine

AU - Holm, Tobias

AU - Zekeng, Elsa Gayle

AU - Cowley, Lauren

AU - Garcia Dorival, Isabel

AU - Doerrbecker, Juliane

AU - Hetzelt, Nicole

AU - Baum, Jonathan H.J.

AU - Portmann, Jasmine

AU - Wölfel, Roman

AU - Gabriel, Martin

AU - Miranda, Osvaldo

AU - Díaz, Graciliano

AU - Díaz, José E.

AU - Fleites, Yoel A.

AU - Piñeiro, Carlos A.

AU - Castro, Carlos M.

AU - Koivogui, Lamine

AU - Magassouba, N’Faly

AU - Diallo, Boubacar

AU - Ruibal, Paula

AU - Oestereich, Lisa

AU - Wozniak, David M.

AU - Lüdtke, Anja

AU - Becker-Ziaja, Beate

AU - Capobianchi, Maria R.

AU - Ippolito, Giuseppe

AU - Carroll, Miles W.

AU - Günther, Stephan

AU - Di Caro, Antonino

AU - Muñoz-Fontela, César

AU - Agrati, Chiara

PY - 2017/5/30

Y1 - 2017/5/30

N2 - 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 CD56brightand CD56dimNK frequency were very low both in fatal and non fatal infections, while a higher frequency of CD56negNK 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.

AB - 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 CD56brightand CD56dimNK frequency were very low both in fatal and non fatal infections, while a higher frequency of CD56negNK 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.

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