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Updated: Mar 30, 2026
Isolation And Dendritic Cell-Uptake of Small Extracellular Vesicles from Echinococcus granulosus
Published on: March 28, 2025
Polyfunctional Specific Response to Echinococcus Granulosus Associates to the Biological Activity of the Cysts
Linda Petrone1, Valentina Vanini1, Elisa Petruccioli1
1Translational Research Unit Department of Epidemiology and Preclinical Research, "L. Spallanzani" National Institute for Infectious Diseases (INMI), Rome, Italy.
Insights
Polyfunctional T-cells producing specific cytokines are linked to active cystic echinococcosis (CE). This finding enhances understanding of CE immunopathogenesis and disease progression in Echinococcus granulosus infections.
Area of Science:
- Immunology
- Parasitology
- Infectious Diseases
Background:
- Cystic echinococcosis (CE) is a parasitic disease caused by Echinococcus granulosus (E. granulosus).
- The immunopathogenesis of CE, particularly the balance between Th1 and Th2 responses, remains incompletely understood.
- Th1 cytokines are associated with resistance, while Th2 cytokines are linked to susceptibility and chronicity in CE.
Purpose of the Study:
- To investigate specific immune signatures in CE patients using multi-parametric flow cytometry (FACS).
- To evaluate the role of CD4+ T-cell cytokine production in relation to CE disease activity.
Main Methods:
- Enrolled 54 subjects with suspected CE, categorizing 42 confirmed CE cases into "active" (25) and "inactive" (17) stages.
- Assessed CD4+ T-cell cytokine production (IFN-γ, IL-2, TNF-α, Th2, IL-10) via FACS after stimulation with E. granulosus Antigen B (AgB).
- Evaluated cytokine profiles in AgB-specific T-cells and response to a mitogen control stimulus.
Main Results:
- No AgB-specific response was detected in the 12 non-CE (NO-CE) subjects.
- CE patients in "active stages" showed significantly higher frequencies of AgB-specific CD4+ T-cells producing IL-2+TNF-α+Th2+ or TNF-α+Th2+ compared to the "inactive stages" group.
- Increased proportions of polyfunctional CD4+ T-cell subsets (triple- and double-functional) were observed in CE patients with active disease.
Conclusions:
- Polyfunctional T-cell subsets, specifically IL-2+TNF-α+Th2+ triple-positive and TNF-α+Th2+ double-positive cells, are associated with the biological activity of CE cysts.
- These findings contribute novel insights into CE immunopathogenesis and disease outcomes, including control and persistence.
- The study highlights the importance of T-cell polyfunctionality in understanding the host response to E. granulosus infection.
Background:
Cystic 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 Findings:
We 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.
Conclusions:
We 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.
