Puthia Manoj K, Sio Selena W S, Lu Jia, Tan Kevin S W
Laboratory of Molecular and Cellular Parasitology, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117597, Singapore.
Infect Immun. 2006 Jul;74(7):4114-23. doi: 10.1128/IAI.00328-06.
Blastocystis is an enteric protozoan purportedly associated with numerous clinical cases of diarrhea, flatulence, vomiting, and other gastrointestinal symptoms. Despite new knowledge of Blastocystis cell biology, genetic diversity, and epidemiology, its pathogenic potential remains controversial. Numerous clinical and epidemiological studies either implicate or exonerate the parasite as a cause of intestinal disease. Therefore, the aim of this study was to investigate the pathogenic potential of Blastocystis by studying the interactions of Blastocystis ratti WR1, an isolate of zoonotic potential, with a nontransformed rat intestinal epithelial cell line, IEC-6. Here, we report that B. ratti WR1 induces apoptosis in IEC-6 cells in a contact-independent manner. Furthermore, we found that B. ratti WR1 rearranges F-actin distribution, decreases transepithelial resistance, and increases epithelial permeability in IEC-6 cell monolayers. In addition, we found that the effects of B. ratti on transepithelial electrical resistance and epithelial permeability were significantly abrogated by treatment with metronidazole, an antiprotozoal drug. Our results suggest for the first time that Blastocystis-induced apoptosis in host cells and altered epithelial barrier function might play an important role in the pathogenesis of Blastocystis infections and that metronidazole has therapeutic potential in alleviating symptoms associated with Blastocystis.
芽囊原虫是一种肠道原生动物，据称与许多腹泻、肠胃胀气、呕吐及其他胃肠道症状的临床病例有关。尽管对芽囊原虫的细胞生物学、遗传多样性和流行病学有了新的认识，但其致病潜力仍存在争议。许多临床和流行病学研究要么认为这种寄生虫是肠道疾病的病因，要么将其排除在外。因此，本研究的目的是通过研究具有人畜共患病潜力的鼠芽囊原虫WR1分离株与未转化的大鼠肠上皮细胞系IEC-6之间的相互作用，来探究芽囊原虫的致病潜力。在此，我们报告鼠芽囊原虫WR1以非接触依赖的方式诱导IEC-6细胞凋亡。此外，我们发现鼠芽囊原虫WR1会重新排列F-肌动蛋白的分布，降低跨上皮电阻，并增加IEC-6细胞单层的上皮通透性。此外，我们发现用抗寄生虫药物甲硝唑处理后，鼠芽囊原虫对跨上皮电阻和上皮通透性的影响会显著消除。我们的结果首次表明，芽囊原虫诱导宿主细胞凋亡和改变上皮屏障功能可能在芽囊原虫感染的发病机制中起重要作用，并且甲硝唑在缓解与芽囊原虫相关的症状方面具有治疗潜力。
