阴道毛滴虫黏附表型和细胞外囊泡影响寄生虫在新型致病机制体内模型中的存活。
Trichomonas vaginalis adherence phenotypes and extracellular vesicles impact parasite survival in a novel in vivo model of pathogenesis.
机构信息
Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, United States of America.
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
出版信息
PLoS Negl Trop Dis. 2023 Oct 23;17(10):e0011693. doi: 10.1371/journal.pntd.0011693. eCollection 2023 Oct.
Trichomonas vaginalis is a human infective parasite responsible for trichomoniasis-the most common, non-viral, sexually transmitted infection worldwide. T. vaginalis resides exclusively in the urogenital tract of both men and women. In women, T. vaginalis has been found colonizing the cervix and vaginal tract while in men it has been identified in the upper and lower urogenital tract and in secreted fluids such as semen, urethral discharge, urine, and prostatic fluid. Despite the over 270 million cases of trichomoniasis annually worldwide, T. vaginalis continues to be a highly neglected organism and thus poorly studied. Here we have developed a male mouse model for studying T. vaginalis pathogenesis in vivo by delivering parasites into the murine urogenital tract (MUT) via transurethral catheterization. Parasite burden was assessed ex-vivo using a nanoluciferase-based gene expression assay which allowed quantification of parasites pre- and post-inoculation. Using this model and read-out approach, we show that T. vaginalis can be found within MUT tissue up to 72 hrs post-inoculation. Furthermore, we also demonstrate that parasites that exhibit increased parasite adherence in vitro also have higher parasite burden in mice in vivo. These data provide evidence that parasite adherence to host cells aids in parasite persistence in vivo and molecular determinants found to correlate with host cell adherence in vitro are applicable to infection in vivo. Finally, we show that co-inoculation of T. vaginalis extracellular vesicles (TvEVs) and parasites results in higher parasite burden in vivo. These findings confirm our previous in vitro-based predictions that TvEVs assist the parasite in colonizing the host. The establishment of this pathogenesis model for T. vaginalis sets the stage for identifying and examining parasite factors that contribute to and influence infection outcomes.
阴道毛滴虫是一种能引起滴虫病的人体感染寄生虫,它是全世界最常见的非病毒性性传播感染。阴道毛滴虫只存在于男性和女性的泌尿生殖道中。在女性中,阴道毛滴虫被发现定植于宫颈和阴道,而在男性中,它存在于上下尿路以及精液、尿道分泌物、尿液和前列腺液等分泌液中。尽管全世界每年有超过 2.7 亿例滴虫病病例,但阴道毛滴虫仍然是一种被高度忽视的生物体,因此研究不足。在这里,我们通过经尿道导管将寄生虫递送至雄性小鼠的泌尿生殖道(MUT),开发了一种用于研究体内阴道毛滴虫发病机制的雄性小鼠模型。通过基于纳米荧光素酶的基因表达测定法,在体外评估寄生虫负荷,该方法允许在接种前和接种后定量寄生虫。使用这种模型和读出方法,我们表明,在接种后 72 小时内,阴道毛滴虫可以在 MUT 组织中被发现。此外,我们还表明,体外寄生虫黏附性增加的寄生虫在体内的寄生虫负荷也更高。这些数据表明,寄生虫对宿主细胞的黏附有助于寄生虫在体内的持续存在,并且在体外与宿主细胞黏附相关的分子决定因素适用于体内感染。最后,我们表明,阴道毛滴虫细胞外囊泡(TvEVs)和寄生虫的共同接种导致体内寄生虫负荷更高。这些发现证实了我们之前基于体外的预测,即 TvEVs 有助于寄生虫定植宿主。这种阴道毛滴虫发病机制模型的建立为鉴定和研究有助于和影响感染结果的寄生虫因素奠定了基础。