Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Key Laboratory of Animal Parasitology of Ministry of Agriculture, 200241, China.
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Key Laboratory of Animal Parasitology of Ministry of Agriculture, 200241, China.
Int J Parasitol. 2019 Apr;49(5):355-364. doi: 10.1016/j.ijpara.2018.11.011. Epub 2019 Feb 22.
Schistosomiasis, caused by trematodes of the genus Schistosoma, remains an important public health issue. Adult schistosomes can survive in the definitive host for several decades, although they are subject to the host immune response. Consequently, understanding the mechanism underlying worm survival in the definitive hosts could aid in developing novel strategies against schistosomiasis. We previously found that an inhibitor of apoptosis in Schistosoma japonicum (SjIAP) could negatively regulate apoptosis by inhibiting caspase activity, which plays a critical role in maintaining tegument integrity. The current study aimed to further analyze the mechanism related to SjIAP governing worm tegument integrity; therefore, we used a yeast two-hybrid screen and identified a series of putative interacting partners of SjIAP, including 14-3-3 (Sj14-3-3) and ubiquitin C (SjUBC). Quantitative real time PCR (qRT-PCR) analysis indicated that transcript profiles of Sj14-3-3 and SjUBC increased together with worm development in definitive hosts, which corresponds to those of SjIAP in S. japonicum. Immunohistochemical analysis showed Sj14-3-3 and SjUBC were located in the tegument of adult parasites while they were also ubiquitously distributed in the bodies of worms. Silencing of Sj14-3-3/SjUBC expression led to increased caspase activity and induced worm death. Inhibition of Sj14-3-3 or SjUBC resulted in significant morphological alterations in the schistosome tegument. Overall, our findings indicated that Sj14-3-3 and SjUBC interacting with SjIAP may belong to another strategy of S. japonicum to maintain the tegument integrity.
血吸虫病是由血吸虫属的吸虫引起的，仍然是一个重要的公共卫生问题。尽管成虫受到宿主免疫反应的影响，但它们可以在终末宿主中存活几十年。因此，了解蠕虫在终末宿主中存活的机制可能有助于开发针对血吸虫病的新策略。我们之前发现，日本血吸虫中的凋亡抑制剂（SjIAP）可以通过抑制半胱天冬酶活性来负调控细胞凋亡，半胱天冬酶活性在维持表皮完整性方面起着关键作用。本研究旨在进一步分析 SjIAP 调控蠕虫表皮完整性的相关机制；因此，我们使用酵母双杂交筛选鉴定了 SjIAP 的一系列潜在相互作用伙伴，包括 14-3-3（Sj14-3-3）和泛素 C（SjUBC）。定量实时 PCR（qRT-PCR）分析表明，Sj14-3-3 和 SjUBC 的转录谱随着终末宿主中蠕虫的发育而增加，与日本血吸虫中的 SjIAP 相对应。免疫组织化学分析表明，Sj14-3-3 和 SjUBC 位于成虫表皮中，而在蠕虫体内也广泛分布。Sj14-3-3/SjUBC 表达沉默导致半胱天冬酶活性增加，并诱导蠕虫死亡。抑制 Sj14-3-3 或 SjUBC 导致血吸虫表皮的显著形态改变。总之，我们的研究结果表明，与 SjIAP 相互作用的 Sj14-3-3 和 SjUBC 可能属于日本血吸虫维持表皮完整性的另一种策略。
