College of Animal Science & Technology, Shihezi University, Shihezi, Xinjiang 832003, China.
State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu 730046, China.
Parasite. 2022;29:16. doi: 10.1051/parasite/2022016. Epub 2022 Mar 22.
Fascioliasis is an important zoonotic helminthic disease caused by Fasciola hepatica and poses a serious threat to global public health. To evade the immune response of its host (humans or animals), F. hepatica secretes various antioxidant enzymes such as glutathione transferase (GST) to facilitate its invasion, migration and parasitism in vivo. To investigate the biological functions of a novel omega-class GST (GSTO), the molecular features of GSTO2 of F. hepatica were analyzed by online software, and the biochemical properties in vitro of recombinant GSTO2 (rGSTO2) were dissected. Then, the regulatory roles of rGSTO2 protein in murine macrophages in vitro were further explored. The results revealed that the GSTO2 gene encodes 254 amino acids, which harbor the characteristic N-terminal domain (βαβαββα) and C-terminal domain (α-helical) of the cytoplasmic GST superfamily. GSTO2 was mainly expressed in F. hepatica vitelline follicles, intestinal tract, excretory pores and vitelline cells, with thioltransferase and dehydroascorbate reductase activities. Moreover, rGSTO2 protein could be taken up by murine macrophages and significantly inhibit the viability of macrophages. In addition, rGSTO2 protein could significantly promote apoptosis and modulate the expression of cytokines in macrophages. These findings suggested that F. hepatica GSTO2 plays an important role in modulating the physiological functions of macrophages, whereby this protein might be involved in immunomodulatory and anti-inflammatory roles during infection. This study provided new insights into the immune-evasion mechanism of F. hepatica and may contribute to the development of a potential anti-inflammatory agent.
肝片形吸虫病是一种重要的人畜共患寄生虫病，由肝片形吸虫引起，对全球公共卫生构成严重威胁。为了逃避宿主（人类或动物）的免疫反应，肝片形吸虫分泌各种抗氧化酶，如谷胱甘肽转移酶（GST），以促进其在体内的入侵、迁移和寄生。为了研究一种新型的ω类 GST（GSTO）的生物学功能，本研究通过在线软件分析了肝片形吸虫 GSTO2 的分子特征，并解析了重组 GSTO2（rGSTO2）的体外生化特性。然后，进一步探讨了 rGSTO2 蛋白在体外对小鼠巨噬细胞的调控作用。结果表明，GSTO2 基因编码 254 个氨基酸，具有细胞质 GST 超家族的特征性 N 端结构域（βαβαββα）和 C 端结构域（α-螺旋）。GSTO2 主要在肝片形吸虫的卵黄滤泡、肠道、排泄孔和卵黄细胞中表达，具有硫转移酶和脱氢抗坏血酸还原酶活性。此外，rGSTO2 蛋白可被小鼠巨噬细胞摄取，并显著抑制巨噬细胞的活力。此外，rGSTO2 蛋白可显著促进巨噬细胞凋亡，并调节巨噬细胞中细胞因子的表达。这些发现表明，肝片形吸虫 GSTO2 在调节巨噬细胞的生理功能方面发挥着重要作用，该蛋白可能在感染过程中参与免疫调节和抗炎作用。本研究为肝片形吸虫的免疫逃避机制提供了新的见解，并可能有助于开发潜在的抗炎药物。
