Fasciola hepatica ESPs Could Indistinctly Activate or Block Multiple Toll-Like Receptors in a Human Monocyte Cell Line.

Fasciola hepatica is a parasitic helminth that induces Th2/Treg responses in its mammalian host. Some reports have suggested that ESPs achieve these polarized immune responses by delaying the activation of dendritic cells and macrophages during the early stages of innate immunity, a process that is mediated by TLR4. The present study aimed to investigate whether TLRs other than TLR4 could also be targeted by F. hepatica ESPs. To achieve this aim a screening system was optimized using THP1-Blue CD14 cells. ESPs were first separated based on their molecular weight and according their net charge by ion exchange chromatography (IEC). Results demonstrated that F. hepatica ESPs mainly cathepsin, serpin and endopin are capable of activating TLR2, TLR4, TLR8 and likely also TLR5 and TLR6. In contrast, fatty acid binding protein strongly suppressed the stimulation induced by various TLR-ligands. Further studies are needed to understand how these apparent contradictory effects of molecules of the same protein mix complement each other in the context of an active infection resulting in the polarized Th2-immune response that characterize F. hepatica infections.