Modulation of Dendritic Cell Maturation by Fasciola hepatica: Implications of Glycans and Mucins for Vaccine Development

Ernesto Rodriguez

doi:10.4172/2157-7560.1000233

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 DCmaturation, 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.

Highlights

Fasciolosis is a major parasitic disease of livestock causing significant economic losses worldwide [1]
In order to evaluate whether F. hepatica glycans play a role in the modulation of the host immune response at a systemic level, we evaluated the ability of spleen cells from infected mice to produce IFNγ when re-stimulated with a total parasite extract presenting intact (FhTE) or oxidized (FhPox) glycans
In agreement with previous results, splenocytes from infected animals stimulated in vitro with F. hepatica total extract (FhTE) produced only IL-5 (Figure 1A). When these cells were stimulated with oxidized FhTE (FhPox) they acquired the capacity of producing IFNγ (Figure 1B), suggesting a role of glycans in the inhibition of IFNγ by specific splenocytes

Summary

Introduction

Fasciolosis is a major parasitic disease of livestock causing significant economic losses worldwide [1]. Fasciolosis is considered an emerging zoonoses with increasing number of people infected around the world [1] In temperate regions this disease is caused by the liver fluke Fasciola hepatica. The parasite is able to modulate the host immune response by increasing the production of IL-4, IL-5, IL-10 or TGFβ[2,6], and inhibiting the levels of IFNγ or IL-17 [2,5]. This strategy allows the parasite establish chronic infections and prolongs its survival in the host. Liver fluke infection has shown to increase susceptibility to other infectious diseases, such as bovine tuberculosis affecting the efficacy of control programs [7]

Methods

Results

Conclusion