Evaluation of the Local Immune Response to Hydatid Cysts in Sheep Liver

SIMPLE SUMMARY: Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by the tapeworm Echinococcus granulosus. Dogs and other carnivores represent the definitive hosts in the life cycle of this parasite, whereas herbivores/omnivores, including humans, are the intermediate hosts, where the larval stage (metacestode) develops in the organs (mainly liver and lungs). Among the intermediate hosts, sheep have recently gained more attention as reservoirs of infection by E. granulosus, but there is still poor information about the local inflammatory response associated with liver cystic echinococcosis. With our study, we aimed to contribute to “finding the gaps” and further define the immunological mechanisms involved during the different stages of the development of ovine hydatidosis. ABSTRACT: In order to characterize the inflammatory phenotype of livers of sheep naturally infected by cystic echinococcosis, 100 sheep livers have been macroscopically assessed for the presence of hydatid cysts and sampled for histopathological and molecular analysis. According to gross and microscopic examination, livers were subsequently classified into three groups: normal liver (Group A), liver with the presence of fertile hydatid cysts (Group B), and liver with the presence of sterile hydatid cysts (Group C). Immunohistochemical analyses were accomplished using primary antibodies anti-Iba1, anti-CD3, anti-CD20, anti-TGF-β, and anti-MMP9. Finally, real-time PCR was performed in order to estimate the concentration levels of tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), interleukin (IL)-12, IL-10, and TGF-β. Immunohistochemical analysis showed a diffuse immunolabelling of mononuclear cells for Iba-1 and TGF-β and a higher amount of CD20+ B cells compared to CD3+ T cells in both Groups B and C. The expression levels of Th-1-like immune cytokines TNF-α, INF-γ, and IL-12 did not show significant statistical differences. However, we found a significant increase in expression levels of Th-2 immune cytokines TGF-β and IL-10 in Groups B and C compared to Group A. Taken together, our findings suggest that macrophages have a predominant role in the local immune response to cystic echinococcosis. Moreover, we can speculate that Th2 immunity may be dominant, corroborating the idea that B cells are decisively essential in the control of the immune response during parasitic infection and that the immunomodulatory role of IL-10 and TGF-β may ensure the persistence of the parasite within the host.