Suppression and modulation of the host immune response to parasitic nematodes have been extensively studied. In the present study, we cloned and produced recombinant phosphotyrosyl phosphatase activator protein from Haemonchus contortus (rHCPTPA), a parasitic nematode of small ruminants, and studied the effect of this protein on modulating the immune response of goat peripheral blood mononuclear cells. Enzymatic assays revealed that rHCPTPA enhanced the p-nitrophenylphosphate phosphatase activity of bovine PP2A₁. Immunohistochemical tests verified that the HCPTPA protein was localised mainly in the bowel wall and on the body surface of worms. It was also shown that serum produced by goats artificially infected with H. contortus successfully recognised rHCPTPA, which conjugated with goat peripheral blood mononuclear cells. The rHCPTPA was then co-incubated with goat peripheral blood mononuclear cells to assess its immunomodulatory effects on proliferation, apoptosis, cytokine secretion, migration and nitric oxide production. Our results showed that rHCPTPA suppressed the proliferation of goat peripheral blood mononuclear cells stimulated by concanavalin A and induced apoptosis in goat peripheral blood mononuclear cells. After rHCPTPA exposure, IFN-γ and IL-2 expression was markedly reduced, whereas secretion of IL-10 and IL-4 was significantly elevated, in goat peripheral blood mononuclear cells. Moreover, rHCPTPA down-regulated nitric oxide production and migration of goat peripheral blood mononuclear cells in a dose-dependent manner. These results illuminate the interaction between parasites and hosts at the molecular level, suggest a possible immunomodulatory target and contribute to the search for innovative proteins that might be candidate targets for drugs and vaccines.

已经广泛研究了宿主对寄生线虫的免疫反应的抑制和调节。在本研究中，我们从小型反刍动物的寄生线虫 Haemonchus contortus (rHCPTPA) 中克隆并生产了重组磷酸酪氨酰磷酸酶激活蛋白，并研究了该蛋白对调节山羊外周血单个核细胞免疫反应的影响。酶促测定表明，rHCPTPA 增强了牛 PP2A ₁的对硝基苯磷酸磷酸酶活性。免疫组织化学测试证实，HCPTPA 蛋白主要定位于肠壁和蠕虫的体表。还表明，人工感染H. contortus 的山羊产生的血清成功识别与山羊外周血单个核细胞结合的rHCPTPA。然后将 rHCPTPA 与山羊外周血单核细胞共培养，以评估其对增殖、细胞凋亡、细胞因子分泌、迁移和一氧化氮产生的免疫调节作用。我们的结果表明，rHCPTPA 抑制了刀豆蛋白 A 刺激的山羊外周血单核细胞的增殖，并诱导了山羊外周血单核细胞的凋亡。在rHCPTPA暴露后，山羊外周血单核细胞中IFN-γ和IL-2的表达显着降低，而IL-10和IL-4的分泌显着升高。此外，rHCPTPA 以剂量依赖性方式下调山羊外周血单核细胞的一氧化氮产生和迁移。