Department of Pathology and Molecular Medicine, McMaster University, Michael G. DeGroote Center for Learning and Discovery, Hamilton, ON L8P 3Z5, Canada.
McMaster Immunology Research Center, McMaster University, Michael G. DeGroote Center for Learning and Discovery, Hamilton, ON L8S 4L8, Canada.
Cells. 2019 Sep 21;8(10):1120. doi: 10.3390/cells8101120.
Approximately 40% of global HIV-1 transmission occurs in the female genital tract (FGT) through heterosexual transmission. Epithelial cells lining the FGT provide the first barrier to HIV-1 entry. Previous studies have suggested that certain hormonal contraceptives or a dysbiosis of the vaginal microbiota can enhance HIV-1 acquisition in the FGT. We examined the effects of lactobacilli and female sex hormones on the barrier functions and innate immune responses of primary endometrial genital epithelial cells (GECs). Two probiotic strains, RC-14 and GR-1, were tested, as were sex hormones estrogen (E2), progesterone (P4), and the hormonal contraceptive medroxyprogesterone acetate (MPA). Our results demonstrate that probiotic lactobacilli enhance barrier function without affecting cytokines. Treatment of GECs with MPA resulted in reduced barrier function. In contrast, E2 treatment enhanced barrier function and reduced production of proinflammatory cytokines. Comparison of hormones plus lactobacilli as a pre-treatment prior to HIV exposure revealed a dominant effect of lactobacilli in preventing loss of barrier function by GECs. In summary, the combination of E2 and lactobacilli had the best protective effect against HIV-1 seen by enhancement of barrier function and reduction in proinflammatory cytokines. These studies provide insights into how probiotic lactobacilli in the female genital microenvironment can alter HIV-1-mediated barrier disruption and how the combination of E2 and lactobacilli may decrease susceptibility to primary HIV infection.
约 40%的全球 HIV-1 传播发生在女性生殖道 (FGT) 中，通过异性传播。生殖道上皮细胞为 HIV-1 进入提供了第一道屏障。先前的研究表明，某些激素避孕药或阴道微生物群落的失调可能会增强 FGT 中的 HIV-1 获得。我们研究了乳杆菌和女性性激素对原代子宫内膜生殖上皮细胞 (GEC) 的屏障功能和先天免疫反应的影响。我们测试了两种益生菌菌株 RC-14 和 GR-1，以及性激素雌激素 (E2)、孕酮 (P4) 和激素避孕药醋酸甲羟孕酮 (MPA)。我们的结果表明，益生菌乳杆菌增强了屏障功能，而不影响细胞因子。MPA 处理 GEC 会导致屏障功能降低。相比之下，E2 处理增强了屏障功能并减少了促炎细胞因子的产生。比较激素加益生菌作为 HIV 暴露前的预处理，发现益生菌在防止 GEC 屏障功能丧失方面具有优势。总之，E2 和益生菌的组合通过增强屏障功能和减少促炎细胞因子的产生，对 HIV-1 具有最佳的保护作用。这些研究提供了关于女性生殖道微环境中的益生菌乳杆菌如何改变 HIV-1 介导的屏障破坏的见解，以及 E2 和益生菌的组合如何降低原发性 HIV 感染的易感性。
