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

Abstract

The liver fluke Fasciola gigantica has a remarkable ability to establish a long-term infection within the hepatobiliary system of the mammalian definitive host. F. gigantica achieves this by producing excretory–secretory molecules, which have immunomodulatory activities. In an effort to elucidate the immunomodulatory functions of F. gigantica thioredoxin peroxidase protein (FgTPx), we expressed recombinant FgTPx (rFgTPx) in Escherichia coli bacteria 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 by F. 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-β), and interferon gamma (IFN-γ), but inhibited PBMC proliferation, migration, and monocyte phagocytosis. Goat PBMCs exposed to 20–40 μg/mL of rFgTPx secreted increased levels of nitric oxide (NO), and 10–40 μg/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.

Proteomic Profiling of the Liver, Hepatic Lymph Nodes, and Spleen of Buffaloes Infected with Fasciola gigantica

“…Protein-protein interactions are key to understanding the mechanisms of interaction between F. gigantica and the host [7,10,12,14,35,36]. We performed prediction analysis to identify the subcellular locations of the DEPs in the liver, hLNs, and spleen (Figure 4A and Table S5).…”

“…Control of fascioliasis in buffaloes is important because buffaloes are considered an economically vital livestock species in many developing countries [7,[11][12][13][14]. Due to the emergence of drug-resistance [15,16], there is a clear need for the development of vaccines and new flukicide drugs to effectively control fascioliasis.…”

Current Status for Controlling the Overlooked Caprine Fasciolosis

“…There have also been in vitro investigations on the function of peripheral blood mononuclear cells (PBMC) after stimulation from F. gigantica thioredoxin (rFgTPx), 14–3-3e (rFg14–3-3e), ras-related rab10 protein (rFgRab10) and cathepsin B (rFgCatB) [ 121 , 122 , 123 , 124 ]. The proteins influenced various functions of PBMC, all capable of binding to PBMC cells, promoting apoptosis, increasing the production of NO and increasing the production of both Th1 and Th2 cytokines, with the exception of rFg14–3-3e.…”

“…rFg14–3-3e may play a role in modulating the Th1/Th2 balance as it increased IL-10 and transforming growth factor-beta expression and lowered IL-4 and IFNγ levels [ 121 ]. Uniquely, rFgRab10 inhibited PBMC proliferation and enhanced migration along with promoting monocyte phagocytosis, while both rFgTPx and rFg14–3-3e suppressed proliferation, migration and phagocytosis [ 121 , 122 , 123 ]. Furthermore, rFgCatB uniquely reduced PBMC cell viability and the authors postulate that knowledge on the function of these proteins could be used to develop a synergistic cocktail vaccine against F. gigantica infection [ 124 ].…”

Fasciola gigantica–Derived Excretory-Secretory Products Alter the Expression of mRNAs, miRNAs, lncRNAs, and circRNAs Involved in the Immune Response and Metabolism in Goat Peripheral Blood Mononuclear Cells

“…To identify the role of these proteins in the long-term survival of F. gigantica, we cloned and expressed the recombinant F. gigantica cathepsin B (rFgCatB), 14-3-3 epsilon (rFg14-3-3e), Ras-related Rab10 (rFgRab10) and thioredoxin peroxidase (rFgTpx) proteins, and characterized their effects on various functions of the goat PBMCs (11)(12)(13)(14). In the related liver fluke F. hepatica, tegumental antigen affects the maturation and antigen presentation to host dendritic cells (DCs) (15).…”