Modulation of the Functions of Goat Peripheral Blood Mononuclear Cells by Fasciola gigantica Thioredoxin Peroxidase In Vitro.

The liver flukeFasciola giganticahas a remarkable ability to establish a long-term infection within the hepatobiliary system of the mammalian definitive host.F. giganticaachieves this by producing excretory-secretory molecules, which have immunomodulatory activities. In an effort to elucidate the immunomodulatory functions ofF. giganticathioredoxin peroxidase protein (FgTPx), we expressed recombinant FgTPx (rFgTPx) inEscherichia colibacteria and examined its effects on several functions of goat peripheral blood mononuclear cells (PBMCs) in vitro. Sequence analysis revealed that FgTPx is related to a thioredoxin-like superfamily. Western blot analysis showed that rFgTPx was recognized by the sera of goats experimentally infected byF. gigantica. The specific binding of rFgTPx protein to the surface of goat PBMCs was demonstrated by immunofluorescence staining. We investigated the influence of serial concentrations of rFgTPx on various functions of goat PBMCs. All concentrations of rFgTPx increased the secretion of interleukin-2 (IL-2), IL-4, IL-10, IL-17, transforming growth factor-beta (TGF-beta), and interferon gamma (IFN-gamma), but inhibited PBMC proliferation, migration, and monocyte phagocytosis. Goat PBMCs exposed to 20-40 mu g/mL of rFgTPx secreted increased levels of nitric oxide (NO), and 10-40 mu g/mL of rFgTPx promoted cell apoptosis. These findings indicate that rFgTPx influences various functions of goat PBMCs by interacting with a large number of cellular targets, ultimately to promote the parasite's survival. The roles of rFgTPx and their interacting proteins warrant further investigation.