Mycoplasma genitalium Rapidly Disseminates to the Upper Reproductive Tracts and Knees of Female Mice following Vaginal Inoculation
Mycoplasma genitalium Rapidly Disseminates to the Upper Reproductive Tracts and Knees of Female Mice following Vaginal Inoculation
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DOI：
10.1128/iai.00840-09
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发表时间：
2010-02-01
影响因子：
3.1
通讯作者：
Pyles, Richard B.
中科院分区：
文献类型：
--
作者：
McGowin, Chris L.;Spagnuolo, Rae Ann;Pyles, Richard B.
生殖支原体是一种新出现的性传播感染，在妇女中与显著的生殖道综合征如宫颈炎、盆腔炎和不孕症有关。由于缺乏完善的小动物生殖道感染模型，对生殖道支原体感染与临床疾病的因果关系的调查在很大程度上受到阻碍。为了建立小鼠模型，雌性瑞士韦氏小鼠分别接受孕酮或雌二醇治疗，然后阴道内接种生殖支原体型菌株G37或当代丹麦菌株M2300。持续下呼吸道感染在接种后77天（d.p.i）被观察到。早在3 d.p.i.时就观察到上生殖道定植，在雌二醇治疗（65%）和黄体酮治疗（18%）的动物中观察到长期感染。在上生殖道，超过90%的生殖支原体pcr阳性样本来自子宫和输卵管。最终，在大约60%的感染动物中观察到21天至10周的总输卵管积水，提示存在输卵管闭塞。此外，生殖支原体早在7 d.p.i时就可传播到膝关节组织，持续感染可达28 d.p.i。感染生殖支原体的小鼠还产生了针对主要抗原外膜蛋白MgPa、延伸因子Tu、丙酮酸脱氢酶E1 α和DnaK （Hsp70）的特异性抗体，表明尽管对感染有强烈的体液反应，但仍会持续感染。这些发现为生殖支原体可建立生殖道和关节组织的长期感染提供了有力的实验证据，并初步证明了生殖道病理结局。
Mycoplasma genitalium is an emerging sexually transmitted infection and in women is associated with notable reproductive tract syndromes such as cervicitis, pelvic inflammatory disease, and infertility. Investigations into the causal relationships of M. genitalium infections and clinical disease have been hindered largely by the lack of a well-established small-animal model of genital tract infection. To establish a murine model, female Swiss Webster mice were conditioned with either progesterone or estradiol and then inoculated intravaginally with M. genitalium type strain G37 or a contemporary Danish strain, M2300. Persistent lower tract infection was observed at up to 77 days postinoculation (d.p.i.). Upper reproductive tract colonization was observed as early as 3 d.p.i., with long-term infection observed in estradiol-treated (65%) and progesterone-treated (18%) animals. In the upper tract, more than 90% of M. genitalium PCR-positive samples were from the uterus and oviducts. Ultimately, gross hydrosalpinx was observed 21 days to 10 weeks p.i. in approximately 60% of infected animals, suggesting the presence of tubal occlusion. In addition, dissemination of M. genitalium to the knee tissues was observed as early as 7 d.p.i., with persistent infection detected at up to 28 d.p.i. Mice infected with M. genitalium also developed specific antibodies to the major antigenic outer membrane protein MgPa, elongation factor Tu, pyruvate dehydrogenase E1 alpha, and DnaK (Hsp70), indicating persistent infection despite robust humoral responses to infection. These findings provide strong experimental evidence that M. genitalium can establish long-term infection of reproductive tract and joint tissues, with preliminary evidence of pathological reproductive tract outcomes.