Modulation of dendritic cell maturation by Fasciola hepatica: Implications of glycans and mucins for vaccine development

Abstract

Fasciola hepatica is a worldwide distributed helminth pathogen that causes great economic losses in sheep and cattle. This parasite is able to regulate the host immune response, producing high levels of IL-5 and low levels of IFN, as well as modulating the function of dendritic cells (DCs), mast cells or macrophages, among others. Moreover, TLR-mediated maturation of DCs can be suppressed by F. hepatica derived components. Here, we investigated the role of glycans in the modulation of LPS-induced maturation of DCs, as wells as in the production of IL-5 and IFN by splenocytes from infected mice. We show that F. hepatica induces the recruitment to the peritoneum of semi-matured DCs, as judged by a down-regulation of MHC class II molecule expression and an increase of CD80 and CD86 expression of DCs in the peritoneum of infected animals. Furthermore, we provide evidence indicating that glycan structures from F. hepatica are responsible, at least in part, for inhibiting LPS-induced DC maturation and production of IFN by splenocytes from infected animals. On the other hand, we show that a mucinlike non-glycosylated peptide highly expressed in NEJ (Fhmuc) is able to synergize with LPS in inducing DC-maturation, and that it induces a T cell response specific for F. hepatica, both alone or in combination with DCs. Our data highlight the role of F. hepatica glycans of in modulating the host immune response and might contribute to the design of vaccines against fasciolosis. © 2014 Noya V et al.