Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health, Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
Trends Microbiol. 2018 Jul;26(7):611-623. doi: 10.1016/j.tim.2017.12.002. Epub 2017 Dec 27.
Chlamydia trachomatis, a leading bacterial cause of sexually transmitted infection-induced infertility, is frequently detected in the gastrointestinal tract. Chlamydia muridarum, a model pathogen for investigating C. trachomatis pathogenesis, readily spreads from the mouse genital tract to the gastrointestinal tract, establishing long-lasting colonization. C. muridarum mutants, despite their ability to activate acute oviduct inflammation, are attenuated in inducing tubal fibrosis and are no longer able to colonize the gastrointestinal tract, suggesting that the spread of C. muridarum to the gastrointestinal tract may contribute to its pathogenicity in the upper genital tract. However, gastrointestinal C. muridarum cannot directly autoinoculate the genital tract. Both antigen-specific CD8 T cells and profibrotic cytokines, such as TNFα and IL-13, are essential for C. muridarum to induce tubal fibrosis; this may be induced by the gastrointestinal C. muridarum, as a second hit, to transmucosally convert tubal repairing - initiated by C. muridarum infection of tubal epithelial cells (serving as the first hit) - into pathogenic fibrosis. Testing the two-hit mouse model should both add new knowledge to the growing list of mechanisms by which gastrointestinal microbes contribute to pathologies in extragastrointestinal tissues and provide information for investigating the potential role of gastrointestinal C. trachomatis in human chlamydial pathogenesis.
沙眼衣原体是导致性传播感染引起不孕的主要细菌病原体，常存在于胃肠道中。鼠型衣原体是研究沙眼衣原体发病机制的模式病原体，它很容易从生殖道传播到胃肠道，并建立持久的定植。尽管鼠型沙眼衣原体突变体能激活急性输卵管炎，但它们在诱导输卵管纤维化方面的毒力减弱，并且不再能够定植于胃肠道，这表明鼠型沙眼衣原体向胃肠道的传播可能有助于其在上生殖道的致病性。然而，胃肠道中的鼠型沙眼衣原体不能直接自体接种生殖道。抗原特异性 CD8 T 细胞和促纤维化细胞因子，如 TNFα 和 IL-13，对于鼠型沙眼衣原体诱导输卵管纤维化是必需的；这可能是由胃肠道中的鼠型沙眼衣原体作为第二次打击，通过粘膜间转换将由鼠型沙眼衣原体感染输卵管上皮细胞（作为第一次打击）引发的输卵管修复转化为致病性纤维化。对两打击小鼠模型的测试不仅应该为越来越多的胃肠道微生物导致肠外组织病理学的机制增加新知识，还应该为研究胃肠道沙眼衣原体在人类衣原体发病机制中的潜在作用提供信息。
