The helminth parasite Fasciola hepatica causes fasciolosis in mammals infecting cattle and sheep, causing significant economic loss to the agricultural community annually. It is also a zoonotic disease, affecting approximately 2.4 million people worldwide. Infection is associated with Th2/Treg immune responses with a direct suppression of Th1/Th17 responses. With a view to understanding how F. hepatica interacts with its host’s immune system we have isolated the tegumental coat antigens (FhTeg) which is a rich source of glycoproteins. Previous studies have examined its interaction with macrophages, mast cells and dendritic cells demonstrating the induction of novel cell populations that fail to drive Th1 immune responses. This thesis advances our understanding of FhTeg by examining its interaction with dendritic cells and CD4+ T-cells and a number of novel findings were identified. The interaction of FhTeg with C-type lectin receptors on dendritic cells is important for its immunomodulatory effect, while mannose glycans are involved, studies in MR knockout mice did not reverse the immune-suppression of FhTeg. We have confirmed that the novel dendritic cells population (CD11clow, MRhigh, CD40low and SOCS3high) induced by FhTeg drives anergic CD4+ T-cells. We also demonstrated for the first time that anergy is associated with F. hepatica infection. More importantly, FhTeg drives these responses and MR is critical for cell to cell communication. We have also demonstrated that FhTeg can directly interact with CD4+ T-cells, enhancing markers of anergy directly and it can suppress cytokine secretion from CD4+ T-cells. Finally, studies on human PBMCs also show a role for FhTegs inhibition, TNF-α was inhibited when PBMCs and CD4+ cells were co-stimulated with both LPS and PMA/Ionomycin but not CD14+ cells. This thesis presents a number of key findings that have never been reported previously in the literature and advance our understanding of helminth immune modulation.