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

Abstract

BackgroundHuman 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 findingsNineteen 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/SignificancesAltogether, 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.

Molecular Determinants of Target Cell Recognition by Human γδ T Cells

“…Multiple lines of evidence since the late 1980s have shown that γδ T cells display strong activities against bacteria, including Mycobacterium tuberculosis ( 76 – 81 ); parasites, such as Plasmodium falciparum ( 82 – 86 ); and viruses ( 87 , 88 ), most notably CMV ( 89 – 91 ).…”

Clinical Characterization of Host Response to Simian Hemorrhagic Fever Virus Infection in Permissive and Refractory Hosts: A Model for Determining Mechanisms of VHF Pathogenesis

“…The data suggest that a potent type 1 interferon response occurs in SHFV-inoculated rhesus monkeys, but it is unclear whether a similar response is present in SHFV-inoculated patas monkeys. NK cell responses are important for survival in human Ebola virus disease cases ( 28 , 29 ). Differences in the timing of NK cell responses are a key difference in non-lethal, mild disease and lethal, severe (Lassa virus) infections in macaques ( 30 ), suggesting the species-specific NK cell responses observed here warrant further exploration.…”

“…PD-1 is associated with T-cell exhaustion and is also found on activated T-cells ( 42 , 43 ). PD-1 + T-cells and CD8 + T-cells appear to play important roles in human cases of Ebola virus disease ( 28 , 29 , 44–46 ). Consequently, it may be fruitful to determine if SHFV provides a means for studying the role of T-cell dysfunction in EVD.…”

Host Transcriptional Response to Ebola Virus Infection

“…Another key finding was the discovery natural killer (NK) cell transcriptional signatures present in mice that survived infection. NK cells have been of interest because of their association with survival of EBOV infections [ 56 , 57 ], thus supporting the transcriptional signature.…”

“…Digital cell quantification (DCQ) analysis of the human data, using the transcriptional response to predict changes in cell populations, highlighted natural killer (NK) cell density increases correlating with survival [ 42 ], a finding that is supported by mouse DCQ analysis of EBOV infection [ 42 ]. NK cells have been shown to be increased in human survivors through FACS analysis [ 57 ]. Importantly, there was no increase in neutrophil markers in humans infected with EBOV, in sharp contrast with data obtained in NHPs.…”