Tian Ai-Ling, Tian Xiaowei, Chen Dan, Lu Mingmin, Calderón-Mantilla Guillermo, Yuan Xiao-Dan, Li Xiangrui, Elsheikha Hany M, Zhu Xing-Quan
State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
Pathogens. 2020 Sep 17;9(9):758. doi: 10.3390/pathogens9090758.
The liver fluke has a remarkable ability to establish a long-term infection within the hepatobiliary system of the mammalian definitive host. achieves this by producing excretory-secretory molecules, which have immunomodulatory activities. In an effort to elucidate the immunomodulatory functions of thioredoxin peroxidase protein (FgTPx), we expressed recombinant FgTPx (rFgTPx) in 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 . 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.
肝吸虫具有在哺乳动物终末宿主的肝胆系统内建立长期感染的显著能力。它通过产生具有免疫调节活性的排泄-分泌分子来实现这一点。为了阐明硫氧还蛋白过氧化物酶蛋白(FgTPx)的免疫调节功能,我们在细菌中表达了重组FgTPx(rFgTPx),并在体外研究了其对山羊外周血单个核细胞(PBMCs)多种功能的影响。序列分析表明,FgTPx与硫氧还蛋白样超家族有关。蛋白质印迹分析表明,rFgTPx可被经[肝吸虫名称未给出]实验感染的山羊血清识别。免疫荧光染色证明了rFgTPx蛋白与山羊PBMCs表面的特异性结合。我们研究了不同浓度的rFgTPx对山羊PBMCs各种功能的影响。所有浓度的rFgTPx均增加了白细胞介素-2(IL-2)、IL-4、IL-10、IL-17、转化生长因子-β(TGF-β)和干扰素-γ(IFN-γ)的分泌,但抑制了PBMC的增殖、迁移和单核细胞吞噬作用。暴露于20 - 40μg/mL rFgTPx的山羊PBMCs分泌的一氧化氮(NO)水平升高,10 - 40μg/mL的rFgTPx促进细胞凋亡。这些发现表明,rFgTPx通过与大量细胞靶点相互作用影响山羊PBMCs的各种功能,最终促进寄生虫的存活。rFgTPx及其相互作用蛋白的作用值得进一步研究。