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

PLoS Negl Trop Dis. 2017 May 30;11(5):e0005645. doi: 10.1371/journal.pntd.0005645. eCollection 2017 May.

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.

MeSH terms

  • Biomarkers / metabolism
  • CD56 Antigen / metabolism
  • CTLA-4 Antigen / metabolism
  • Databases, Factual
  • Ebolavirus
  • Female
  • Flow Cytometry
  • Guinea / epidemiology
  • Hemorrhagic Fever, Ebola / immunology*
  • Hemorrhagic Fever, Ebola / mortality*
  • Humans
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation / immunology
  • Male
  • Natural Cytotoxicity Triggering Receptor 1 / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, KIR2DL1 / metabolism
  • T-Lymphocyte Subsets / immunology*
  • Viral Load
  • fas Receptor / metabolism

Substances

  • Biomarkers
  • CD56 Antigen
  • CTLA-4 Antigen
  • FAS protein, human
  • NCR1 protein, human
  • Natural Cytotoxicity Triggering Receptor 1
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, KIR2DL1
  • fas Receptor

Grants and funding

This work was founded by: - the project EVIDENT (Ebola virus disease: correlates of protection, determinants of outcome, and clinical management) that received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 666100. Recipients: SG - service contract IFS/2011/272-372 funded by Directorate-General for International Cooperation and Development. Recipients: SG - MInistry of Health (Italy "Ricerca Corrente Program". Recipient: GI AL is a recipient of a pre-doctoral fellowship from the Leibniz Center of Infection. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.