Molecular Biology Institute, University of California, Los Angeles, California, United States of America.
PLoS Pathog. 2013;9(7):e1003482. doi: 10.1371/journal.ppat.1003482. Epub 2013 Jul 11.
Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogential tract where it remains extracellular and adheres to epithelial cells. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Here, we use a combination of methodologies including cell fractionation, immunofluorescence and electron microscopy, RNA, proteomic and cytokine analyses and cell adherence assays to examine pathogenic properties of T. vaginalis. We have found that T.vaginalis produces and secretes microvesicles with physical and biochemical properties similar to mammalian exosomes. The parasite-derived exosomes are characterized by the presence of RNA and core, conserved exosomal proteins as well as parasite-specific proteins. We demonstrate that T. vaginalis exosomes fuse with and deliver their contents to host cells and modulate host cell immune responses. Moreover, exosomes from highly adherent parasite strains increase the adherence of poorly adherent parasites to vaginal and prostate epithelial cells. In contrast, exosomes from poorly adherent strains had no measurable effect on parasite adherence. Exosomes from parasite strains that preferentially bind prostate cells increased binding of parasites to these cells relative to vaginal cells. In addition to establishing that parasite exosomes act to modulate host∶parasite interactions, these studies are the first to reveal a potential role for exosomes in promoting parasite∶parasite communication and host cell colonization.
阴道毛滴虫是一种常见的性传播寄生虫,它在人类泌尿生殖道中定植,保持细胞外状态并黏附在上皮细胞上。感染的严重程度因宿主和寄生虫株而异,从无症状到高度炎症不等。在这里,我们结合使用了细胞分离、免疫荧光和电子显微镜、RNA、蛋白质组学和细胞因子分析以及细胞黏附测定等多种方法,来研究阴道毛滴虫的致病特性。我们发现,阴道毛滴虫产生并分泌具有类似于哺乳动物外泌体的物理和生化特性的微泡。寄生虫来源的外泌体的特征在于存在 RNA 和核心保守的外泌体蛋白以及寄生虫特异性蛋白。我们证明,阴道毛滴虫外泌体可以与宿主细胞融合并将其内容物传递给宿主细胞,并调节宿主细胞的免疫反应。此外,来自高黏附性寄生虫株的外泌体增加了低黏附性寄生虫对阴道和前列腺上皮细胞的黏附。相比之下,低黏附性株的外泌体对寄生虫黏附没有可测量的影响。优先结合前列腺细胞的寄生虫株的外泌体增加了这些细胞相对于阴道细胞的寄生虫结合。除了证实寄生虫外泌体可调节宿主与寄生虫的相互作用外,这些研究还首次揭示了外泌体在促进寄生虫与寄生虫之间的通信和宿主细胞定植方面的潜在作用。