National Reference Laboratory for Animal Schistosomiasis, Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, PR China.
College of Life Sciences, Shanghai Normal University, Shanghai, PR China.
Int J Parasitol. 2022 Jul;52(8):569-579. doi: 10.1016/j.ijpara.2022.01.005. Epub 2022 Mar 19.
Schistosomiasis is a globally important helminthic disease of both humans and animals, and is the second most common parasitic disease after malaria. Although praziquantel is extensively used for treatment of parasitic diseases, drug resistance has been reported. Therefore, new drugs and effective vaccines are needed for continuous control of schistosomiasis. Eggs produced by schistosomes are responsible for the occurrence and spread of schistosomiasis. Revealing the reproductive mechanism of schistosomes will help to control this disease. In this study, the proteomic profiles of single-sex infected female worms and bisexual infected mature female worms of Schistosoma japonicum at 18, 21, 23 and 25 days p.i. were identified with isobaric tags for relative quantitation-coupled liquid chromatography-tandem mass spectrometry. Differentially expressed proteins were subsequently used for bioinformatic analysis. Six highly expressed differentially expressed proteins in mature female worms were selected and long-term interference with small interfering RNA (siRNA) was conducted to determine biological functions. SiRNA against S. japonicum translationally controlled tumour protein (SjTCTP) resulted in the most significant effect on the growth and development of MF worms. Sjtctp mRNA expression gradually increased over time with a high level of expression maintained at 25-42 days p.i., while levels were significantly higher in mature female worms than male and SF worms. The subsequent animal immune protection experiments showed that recombinant SjTCTP (rSjTCTP) reduced the number of adults by 44.7% (P < 0.01), average egg burden per gram of liver by 57.94% (P < 0.01), egg hatching rate by 47.57% (P < 0.01), and oviposition of individual females by 43.16%. rSjTCTP induced higher levels of serum IgG, IL-2, and IL-10 in mice. Collectively, these results show that SjTCTP is vital to reproduction of female worms and, thus, is a candidate antigen for immune protection.
日本血吸虫病是一种全球性重要的人兽共患蠕虫病，是仅次于疟疾的第二大常见寄生虫病。虽然吡喹酮被广泛用于治疗寄生虫病，但已有耐药性报道。因此，需要新的药物和有效的疫苗来持续控制血吸虫病。血吸虫产生的虫卵是血吸虫病发生和传播的原因。揭示血吸虫的生殖机制将有助于控制这种疾病。在这项研究中，采用相对定量同位素标记与液相色谱-串联质谱联用技术（iTRAQ-LC-MS/MS）鉴定了感染后 18、21、23 和 25 天的日本血吸虫单性雌虫和两性成熟雌虫的蛋白质组谱。随后对差异表达蛋白进行了生物信息学分析。选择了在成熟雌虫中高表达的 6 个差异表达蛋白，并进行了小干扰 RNA（siRNA）的长期干扰实验，以确定其生物学功能。针对日本血吸虫翻译控制肿瘤蛋白（SjTCTP）的 siRNA 对 MF 蠕虫的生长和发育影响最为显著。Sjtctp mRNA 表达随时间逐渐增加，在感染后 25-42 天表达水平维持在较高水平，而在成熟雌虫中的表达水平明显高于雄虫和 SF 蠕虫。随后的动物免疫保护实验表明，重组 SjTCTP（rSjTCTP）使成虫数量减少 44.7%（P<0.01），肝内每克卵的负担减少 57.94%（P<0.01），卵孵化率减少 47.57%（P<0.01），个体雌虫的产卵量减少 43.16%。rSjTCTP 诱导了小鼠血清 IgG、IL-2 和 IL-10 水平的升高。综上所述，这些结果表明 SjTCTP 对雌虫的繁殖至关重要，因此是免疫保护的候选抗原。
