Xu Jian-Bang, Lu Shen-Jiao, Ke Li-Jiao, Qiu Zhuo-Er, Chen Lei, Zhang Hao-Li, Wang Xi-Yuan, Wei Xiao-Fan, He Shuming, Zhu Yun-Xin, Lun Zhao-Rong, Zhou Wen-Liang, Zhang Yi-Lin
School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
PLoS Negl Trop Dis. 2021 Apr 16;15(4):e0009319. doi: 10.1371/journal.pntd.0009319. eCollection 2021 Apr.
Trichomonas vaginalis is a common protozoan parasite, which causes trichomoniasis associated with severe adverse reproductive outcomes. However, the underlying pathogenesis has not been fully understood. As the first line of defense against invading pathogens, the vaginal epithelial cells are highly responsive to environmental stimuli and contribute to the formation of the optimal luminal fluid microenvironment. The cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel widely distributed at the apical membrane of epithelial cells, plays a crucial role in mediating the secretion of Cl- and HCO3-. In this study, we investigated the effect of T. vaginalis on vaginal epithelial ion transport elicited by prostaglandin E2 (PGE2), a major prostaglandin in the semen. Luminal administration of PGE2 triggered a remarkable and sustained increase of short-circuit current (ISC) in rat vaginal epithelium, which was mainly due to Cl- and HCO3- secretion mediated by the cAMP-activated CFTR. However, T. vaginalis infection significantly abrogated the ISC response evoked by PGE2, indicating impaired transepithelial anion transport via CFTR. Using a primary cell culture system of rat vaginal epithelium and a human vaginal epithelial cell line, we demonstrated that the expression of CFTR was significantly down-regulated after T. vaginalis infection. In addition, defective Cl- transport function of CFTR was observed in T. vaginalis-infected cells by measuring intracellular Cl- signals. Conclusively, T. vaginalis restrained exogenous PGE2-induced anion secretion through down-regulation of CFTR in vaginal epithelium. These results provide novel insights into the intervention of reproductive complications associated with T. vaginalis infection such as infertility and disequilibrium in vaginal fluid microenvironment.
阴道毛滴虫是一种常见的原生动物寄生虫,可导致与严重不良生殖结局相关的滴虫病。然而,其潜在的发病机制尚未完全明确。作为抵御入侵病原体的第一道防线,阴道上皮细胞对环境刺激高度敏感,并有助于形成最佳的管腔液微环境。囊性纤维化跨膜传导调节因子(CFTR)是一种广泛分布于上皮细胞顶端膜的阴离子通道,在介导氯离子(Cl-)和碳酸氢根离子(HCO3-)的分泌中起关键作用。在本研究中,我们调查了阴道毛滴虫对由前列腺素E2(PGE2,精液中的一种主要前列腺素)引发的阴道上皮离子转运的影响。向管腔中施用PGE2可引发大鼠阴道上皮短路电流(ISC)显著且持续增加,这主要归因于由环磷酸腺苷(cAMP)激活的CFTR介导的Cl-和HCO3-分泌。然而,阴道毛滴虫感染显著消除了PGE2诱发的ISC反应,表明通过CFTR的跨上皮阴离子转运受损。使用大鼠阴道上皮原代细胞培养系统和人阴道上皮细胞系,我们证明阴道毛滴虫感染后CFTR的表达显著下调。此外,通过测量细胞内Cl-信号,在阴道毛滴虫感染的细胞中观察到CFTR的Cl-转运功能存在缺陷。总之,阴道毛滴虫通过下调阴道上皮中的CFTR来抑制外源性PGE2诱导的阴离子分泌。这些结果为干预与阴道毛滴虫感染相关的生殖并发症(如不孕症和阴道液微环境失衡)提供了新的见解。