With near surface expression of FhGST-S1, in the parenchyma and tegument, there is the potential for this enzyme to be readily released into the host environment. Indeed, we have identified FhGST-S1 in the ES products of adult worms. With this in mind, previous studies have highlighted the importance of parasite Sigma class GSTs in immunomodulation of the host immune response. This includes our recent study implicating rFhGST-S1 in chronic inflammation through the activation of dendritic cells (DCs) [48] . While active rFhGST-S1 was able to induce levels of IL-12p40 and IL-6 cytokines in DCs in a dose-dependent manner, the previously described F. hepatica Mu-class GSTs failed to induce any cytokine secretion. Since denatured rFhGST-S1 also failed to induce any cytokines in DCs, activation of DCs is likely related to the structure and activity of the enzyme. However, inhibition of nitric oxide production, involved in driving a Th2 immune response, may also be a contributing factor in skewing the host response to fasciolosis [60] .