Fasciola hepatica, a highly prevalent helminth parasite in Uruguay, is responsible for significant economic losses linked to livestock production, mainly bovine meat and dairy production. The problem of fasciolosis has increased due to parasite resistance to anthelmintic drugs. Furthermore, despite the availability of drugs, such as triclabendazole (TCZ), for the treatment of fasciolosis, it does not prevent the disease, liver damage, or parasitic reinfection. On the other hand, infected animals present a strong immunoregulation induced by the parasite, making the development of vaccines difficult and increasing susceptibility to secondary infections. One of the alternatives is to identify molecular targets in the host that allow us to associate the severity of the disease with molecules expressed by the natural host. In this sense, our work has sought to identify and evaluate immunoregulatory mechanisms deployed by the parasite. This thesis is divided into two parts: inthe first instance, we use an experimental murine infection model, and in the second, we study the infestation in a natural host (bovine). The murine experimental model has allowed us to analyze the immune system in detail, finding that the parasite regulates the host immune system by inducing Th2 and regulatory T immunity (Treg) through the overexpression of heme oxygenase 1 (HO-1). In peritoneal antigen-presenting cells (APC). HO-1 is involved in heme catabolism and has antioxidant and immunoregulatory properties. Furthermore, HO-1+ APCs also express a receptor of the innate immune system (MGL2) that recognizes carbohydrates of parasitic origin and modulates the induction of the adaptive immune response. By inhibiting HO-1 activity, we detected increased production of reactive oxygen and nitrogen species (ROS/RNS) in peritoneal APCs and decreased mice susceptibility to parasitic infection. As an alternative strategy to evaluate the role of F4/80+ HO-1+ cells in infection, we used MGL2-DTR transgenic mice, which encode the diphtheria toxin receptor in MGL2+ cells. In this study, we demonstrate that peritoneal APCs during infection favor parasite survival, which is mediated by the induction of splenic Tregs in vivo. Depletion of MGL2+ cells conferred partial resistance to infection in mice and abrogated the parasite-induced increasein Tregs, demonstrating that MGL2+ (F4/80+ HO-1+) cells are critical for F. hepatica infection and could constitute immunological checkpoints to control parasite infection. In this thesis, we also characterize the anti-parasitic immune response in experimentally infected cattle and evaluate the effect of the parasite on vaccine-induced immunity. We detected that the parasite generates significant liver damage, analyzed indirectly through the levels of liver enzymesin vivo and by an evaluation score at slaughter. TCZ treatment reduced parasite burden and liverdamage but could not eliminate all parasites, and liver damage persisted. In addition, we investigated the cellular response generated by the infection, and we found that at 43 days postinfection (dpi), there is an increase in CD4+ and CD21+ cells in infected animals. The percentage of CD11c+ cells does not differ between the groups. When the humoral and cellular immune response was investigated, we found that specific antibodies against F. hepatica remained elevated during the first 12 weeks of infection. However, in the chronic phase of infection, antibody levels decreased considerably. The treatment with TCZ affects the quantity and quality of specific antibodies against F. hepatica. The TCZ also increases the levels of IFN-γ, IL-10, and IL-4 in the liver. Finally, we studied the impact of the parasite on the adaptive immune response generated by vaccination against Clostridium spp and foot-and-mouth disease virus (FMDV) during the acute stage and against respiratory pathogens (Pasteurella multocida and Mannheimia haemolytica) in the chronic stage. At 43 dpi, the animals in the infected group presented a decrease in the levels of IgG antibodies against Clostridium spp. We also found that IgG1 levels against FMDV decreased significantly in infected animals at 28 dpi and presented a lower avidity than antibodies from uninfected animals. In the same sense, when evaluating the respiratory vaccine, we found that infected animals showed lower levels of specific antibodies against M. haemolytica than thosefrom the control group. Interestingly, TCZ treatment restored vaccine antibody titers. However, P.multocida-specific IgG decreased both in the infected group of animals at 213 dpi. In conclusion, this thesis provides knowledge about the immunoregulatory mechanisms generated by F. hepatica in two experimental models of infection, contributing to the identification of strategic targets for the control of infection by this parasite and the importance of the immunomodulation generated by the parasite in vaccine-triggered immunity in cattle.