Mechanisms of Immune Modulation by Fasciola Hepatica: The Impact of Innate Immune Cells on the Developing Adaptive Immune Response

Fasciola (F.) hepatica lives for prolonged periods within its host due to its ability to modulate host immune responses. Unlike other helminths, within hours postinfection it drives antigen specific Th2/Treg responses. This polarisation of the host immune response continues throughout all developmental stages within the definitive host. Central to the parasite’s ability to produce such an immune outcome is the secretion of a plethora of molecules that interact with innate immune cells impairing their ability to promote Th1/Th17 responses. This firmly establishes F. hepatica as an important model to examine the anti-inflammatory properties of helminths. In this chapter, we specifically examine the communication between the secreted and shed molecules from F. hepatica and dendritic cells, macrophages and mast cells. In particular, we aim to highlight the impact that this interaction has on the development of Th1/Th17 immune responses. This chapter examines the diverse range of F. hepatica molecules that utilise different immune mechanisms to achieve the same overall outcome, thus ensuring redundancy in the development of Th2/Treg immune responses associated with F. hepatica infection.

Keywords: Fasciola hepatica, Th1, Th2, Treg, dendritic cells, macrophages, mast cells, IL-4, IL-10, IL-5, excretory-secretory molecules, tegumental antigens, cathepsin L, peroxredoxin, human defence molecule, sigma Class Glutathione transferase, immune modulatory molecules.