Olmos-Ortiz L M, Barajas-Mendiola M A, Barrios-Rodiles M, Castellano L E, Arias-Negrete S, Avila E E, Cuéllar-Mata P
Departamento de Biología, Universidad de Guanajuato, Guanajuato, Mexico.
Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Parasite Immunol. 2017 Jun;39(6). doi: 10.1111/pim.12426. Epub 2017 May 4.
Trichomonas vaginalis (Tv) is a flagellated parasite commonly spread through sexual transmission. This protozoan initiates a severe inflammatory process, inducing nitric oxide, interleukin-6 (IL-6), IL-8, IL-10, IL-17 and IL-22 production by host immune cells. The parasites elicit these responses by releasing surface lipophosphoglycan, small extracellular vesicles (exosomes) and other factors. Tv exosomes are similar to mammalian exosomes and have been implicated in the modulation of IL-8 secretion by epithelial cells. Here, we report that exosome-like vesicles from T. vaginalis (Tv-ELVs) induced a more than 15-fold increase in IL-10 expression in RAW264.7 macrophages but only a two fold increase in IL-6 and TNF-α expression levels measured by RT-PCR. Because Tv-ELVs modulated the macrophage response, we also explored the effect of Tv-ELVs in a murine model of infection. Pretreatment with Tv-ELVs significantly increased IL-10 production as measured in vaginal washes by days 8 and 16 post-infection. Remarkably, Tv-ELVs-pretreated mice exhibited a decrease in IL-17 production and a significant decrease in vulvar inflammation. In addition, IL-6 and IL-13 were decreased during infection. Our results suggest that Tv-ELVs have an immunomodulatory role on the cytokine profile induced by the parasite and promote a decrease in the inflammatory process in mice infected with T. vaginalis.
阴道毛滴虫（Tv）是一种通过性传播的鞭毛虫寄生虫。这种原生动物引发严重的炎症过程，诱导宿主免疫细胞产生一氧化氮、白细胞介素-6（IL-6）、IL-8、IL-10、IL-17和IL-22。寄生虫通过释放表面脂磷壁酸、小细胞外囊泡（外泌体）和其他因子引发这些反应。Tv外泌体与哺乳动物外泌体相似，并参与上皮细胞对IL-8分泌的调节。在此，我们报告来自阴道毛滴虫的类外泌体囊泡（Tv-ELVs）在RAW264.7巨噬细胞中诱导IL-10表达增加超过15倍，但通过RT-PCR检测到IL-6和TNF-α表达水平仅增加两倍。由于Tv-ELVs调节巨噬细胞反应，我们还在小鼠感染模型中探索了Tv-ELVs的作用。感染后第8天和第16天，通过阴道灌洗测量，用Tv-ELVs预处理显著增加了IL-10的产生。值得注意的是，用Tv-ELVs预处理的小鼠IL-17产生减少，外阴炎症显著减轻。此外，感染期间IL-6和IL-13减少。我们的结果表明，Tv-ELVs对寄生虫诱导的细胞因子谱具有免疫调节作用，并促进感染阴道毛滴虫的小鼠炎症过程的减轻。
