Molecular Parasitology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
Parasitology Laboratory, School of Animal Medicine, Northeast Agricultural University, HarBin 150030, China.
Int J Mol Sci. 2018 Aug 16;19(8):2426. doi: 10.3390/ijms19082426.
To further investigate the importance of acetylcholinesterase (SjAChE) in cholinergic signaling for parasite growth and development, we used RNA interference (RNAi) to knock-down its expression in adults and eggs in vitro. This resulted in its reduced transcription but also expression of other important genes involved both in cholinergic signaling and glucose uptake were impacted substantially. Significant decreases in AChE protein expression, AChE enzymatic activity, and glucose uptake were observed in the -knockdown parasites compared with luciferase controls. In vaccine/challenge experiments, we found that immunization of mice with recombinant SjAChE (rSjAChE) expressed in elicited reductions in male worm numbers (33%), liver granuloma density (41%), and reduced numbers of mature intestinal eggs (73%) in the vaccinated group compared with the control group. These results indicate AChE plays an important role in the metabolism of male worms, and impacts indirectly on female fecundity leading to increased numbers of immature eggs being released and reduced sizes of liver granulomas. Furthermore, cytokine analysis showed that immunization of mice with rSjAChE elicited a predominantly Th1-type immune response characterized by increased production of IFNγ in splenic CD4⁺ T cells of vaccinated mice. The study confirms the potential of SjAChE as a vaccine/drug candidate against zoonotic schistosomiasis japonica.
为了进一步研究乙酰胆碱酯酶（SjAChE）在寄生虫生长和发育中的胆碱能信号传导中的重要性，我们使用 RNA 干扰（RNAi）在体外将其在成虫和卵中的表达敲低。这导致其转录减少，但也影响了涉及胆碱能信号传导和葡萄糖摄取的其他重要基因的表达。与荧光素酶对照相比，在 -敲低寄生虫中观察到 AChE 蛋白表达、AChE 酶活性和葡萄糖摄取显著降低。在疫苗/挑战实验中，我们发现用重组 SjAChE（rSjAChE）免疫小鼠可导致雄性蠕虫数量减少（33%），肝肉芽肿密度降低（41%），以及成熟肠道卵数量减少（73%）在接种组与对照组相比。这些结果表明 AChE 在雄性蠕虫的代谢中起重要作用，并间接影响雌性生育力，导致未成熟卵的数量增加和肝肉芽肿的大小减小。此外，细胞因子分析表明，用 rSjAChE 免疫小鼠可引发以 IFNγ 在接种小鼠脾 CD4⁺T 细胞中产生增加为特征的 Th1 型免疫应答。该研究证实 SjAChE 作为针对人畜共患日本血吸虫病的疫苗/药物候选物的潜力。
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