Polyfunctional Specific Response to Echinococcus Granulosus Associates to the Biological Activity of the Cysts.

Linda Petrone,Vincenzo Schininà,Delia Goletti,Valentina Vanini,Giuseppe Maria Ettorre,Antonella Teggi,Edoardo Pozio,Alessandra Ludovisi,Angela Corpolongo,Elisa Busi Rizzi,Giuseppe Ippolito,Elisa Petruccioli,Aysegul Taylan Ozkan

doi:10.1371/journal.pntd.0004209

Abstract

BackgroundCystic echinococcosis (CE) is a complex disease caused by Echinococcus granulosus (E.granulosus), and its immunophatogenesis is still not clearly defined. A peculiar feature of chronic CE is the coexistence of Th1 and Th2 responses. It has been suggested that Th1 cytokines are related to disease resistance, whereas Th2 cytokines are related to disease susceptibility and chronicity. The aim of this study was to evaluate, by multi-parametric flow cytometry (FACS), the presence of CE specific immune signatures.Methodology/Principal FindingsWe enrolled 54 subjects with suspected CE; 42 of them had a confirmed diagnosis, whereas 12 were classified as NO-CE. Based on the ultrasonography images, CE patients were further categorized as being in "active stages" (25) and "inactive stages" (17). The ability of CD4+ T-cells to produce IFN-γ, IL-2, TNF-α, Th2 cytokines or IL-10 was assessed by FACS on antigen-specific T-cells after overnight stimulation with Antigen B (AgB) of E.granulosus. Cytokine profiles were evaluated in all the enrolled subjects. The results show that none of the NO-CE subjects had a detectable AgB-specific response. Among the CE patients, the frequency and proportions of AgB-specific CD4+ T-cells producing IL-2+TNF-α+Th2+ or TNF-α+Th2+ were significantly increased in the “active stages” group compared to the “inactive stages” group. Moreover, an increased proportion of the total polyfunctional subsets, as triple-and double-functional CD4 T-cells, was found in CE patients with active disease. The response to the mitogen, used as a control stimulus to evaluate the immune competence status, was characterized by the same cytokine subsets in all the subjects enrolled, independent of CE.ConclusionsWe demonstrate, for the first time to our knowledge, that polyfunctional T-cell subsets as IL-2+TNF-α+Th2+ triple-positive and TNF-α+Th2+ double-positive specific T-cells associate with cyst biological activity. These results contribute to increase knowledge of CE immunophatogenesis and the disease outcome in terms of control and persistence.

Highlights

Cystic echinococcosis (CE) is a widespread zoonosis caused by the larval stage of the tapeworm Echinococcus granulosus (E.granulosus) [1].CE is a complex disease, and several aspects, such as its natural history, parasite-host interplay, poor response to treatment, and predisposition to persistence are still not clearly defined.An important question is how the parasite may influence the quality of the host’s immune response
For the first time to our knowledge, that polyfunctional T-cell subsets as IL2+TNF-α+Th2+ triple-positive and TNF-α+Th2+ double-positive specific T-cells associate with cyst biological activity
It has been suggested that Th1 cytokines are related to disease resistance and in contrast, Th2 cytokines are associated with disease susceptibility and chronicity [2]; high levels of Th1 cytokines are found in patients who were successfully responding to treatment, whereas high levels of IL4 and IL-10 occur in patients who did not [3,4,5]

Summary

Introduction

Cystic echinococcosis (CE) is a widespread zoonosis caused by the larval stage of the tapeworm Echinococcus granulosus (E.granulosus) [1].CE is a complex disease, and several aspects, such as its natural history, parasite-host interplay, poor response to treatment, and predisposition to persistence are still not clearly defined.An important question is how the parasite may influence the quality of the host’s immune response. It has been suggested that Th1 cytokines are related to disease resistance and in contrast, Th2 cytokines are associated with disease susceptibility and chronicity [2]; high levels of Th1 cytokines are found in patients who were successfully responding to treatment, whereas high levels of IL4 and IL-10 occur in patients who did not [3,4,5]. This result indicates that the IL-10/IL-4 endogenous production induced by CE may impair Th1 response, allowing for E. granulosus persistence [6]. The aim of this study was to evaluate, by multi-parametric flow cytometry (FACS), the presence of CE specific immune signatures

Objectives

Methods

Results

Conclusion