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Antigen Presenting Cells Link the Female Genital Tract Microbiome to Mucosal Inflammation, With Hormonal Contraception as an Additional Modulator of Inflammatory Signatures
Frontiers in Cellular and Infection Microbiology ( IF 4.6 ) Pub Date : 2021-09-16 , DOI: 10.3389/fcimb.2021.733619
Elizabeth H Byrne 1, 2 , Mara Farcasanu 1 , Seth M Bloom 1, 2, 3 , Nondumiso Xulu 4 , Jiawu Xu 1 , Barry L Hykes 5 , Nomfuneko A Mafunda 1 , Matthew R Hayward 1, 2 , Mary Dong 1, 6 , Krista L Dong 1, 2, 6 , Thandeka Gumbi 6, 7 , Fransisca Xolisile Ceasar 6, 7 , Nasreen Ismail 4 , Thumbi Ndung'u 1, 4, 8, 9, 10 , Christina Gosmann 1, 2 , Musie S Ghebremichael 1, 2 , Scott A Handley 5 , Caroline M Mitchell 1, 2, 11 , Alexandra-Chloé Villani 2, 12, 13 , Douglas S Kwon 1, 2, 3
Affiliation  

The microbiome of the female genital tract (FGT) is closely linked to reproductive health outcomes. Diverse, anaerobe-dominated communities with low Lactobacillus abundance are associated with a number of adverse reproductive outcomes, such as preterm birth, cervical dysplasia, and sexually transmitted infections (STIs), including HIV. Vaginal dysbiosis is associated with local mucosal inflammation, which likely serves as a biological mediator of poor reproductive outcomes. Yet the precise mechanisms of this FGT inflammation remain unclear. Studies in humans have been complicated by confounding demographic, behavioral, and clinical variables. Specifically, hormonal contraception is associated both with changes in the vaginal microbiome and with mucosal inflammation. In this study, we examined the transcriptional landscape of cervical cell populations in a cohort of South African women with differing vaginal microbial community types. We also investigate effects of reproductive hormones on the transcriptional profiles of cervical cells, focusing on the contraceptive depot medroxyprogesterone acetate (DMPA), the most common form of contraception in sub-Saharan Africa. We found that antigen presenting cells (APCs) are key mediators of microbiome associated FGT inflammation. We also found that DMPA is associated with significant transcriptional changes across multiple cell lineages, with some shared and some distinct pathways compared to the inflammatory signature seen with dysbiosis. These results highlight the importance of an integrated, systems-level approach to understanding host-microbe interactions, with an appreciation for important variables, such as reproductive hormones, in the complex system of the FGT mucosa.



中文翻译:

抗原呈递细胞将女性生殖道微生物群与粘膜炎症联系起来,激素避孕作为炎症特征的额外调节剂

女性生殖道 (FGT) 的微生物组与生殖健康结果密切相关。以厌氧菌为主的多样性社区乳酸菌大量与许多不利的生殖结果有关,例如早产、宫颈发育不良和性传播感染 (STI),包括 HIV。阴道生态失调与局部粘膜炎症有关,这可能是导致不良生殖结果的生物介质。然而,这种 FGT 炎症的确切机制仍不清楚。由于混淆了人口统计学、行为和临床变量,对人类的研究变得复杂。具体而言,激素避孕与阴道微生物群的变化和粘膜炎症有关。在这项研究中,我们检查了一组具有不同阴道微生物群落类型的南非女性中宫颈细胞群的转录情况。我们还研究了生殖激素对宫颈细胞转录谱的影响,重点关注避孕药库醋酸甲羟孕酮 (DMPA),这是撒哈拉以南非洲最常见的避孕形式。我们发现抗原呈递细胞 (APC) 是微生物组相关 FGT 炎症的关键介质。我们还发现 DMPA 与多个细胞谱系的显着转录变化相关,与生态失调所见的炎症特征相比,有一些共享的和一些不同的途径。这些结果强调了一种综合的、系统级的方法来理解宿主-微生物相互作用的重要性,同时对 FGT 粘膜复杂系统中的重要变量(如生殖激素)进行了评估。专注于避孕药库醋酸甲羟孕酮 (DMPA),这是撒哈拉以南非洲最常见的避孕方式。我们发现抗原呈递细胞 (APC) 是微生物组相关 FGT 炎症的关键介质。我们还发现 DMPA 与跨多个细胞谱系的显着转录变化相关,与生态失调所见的炎症特征相比,有一些共享的和一些不同的途径。这些结果强调了一种综合的、系统级的方法来理解宿主-微生物相互作用的重要性,同时对 FGT 粘膜复杂系统中的重要变量(如生殖激素)进行了评估。专注于避孕药库醋酸甲羟孕酮 (DMPA),这是撒哈拉以南非洲最常见的避孕方式。我们发现抗原呈递细胞 (APC) 是微生物组相关 FGT 炎症的关键介质。我们还发现 DMPA 与跨多个细胞谱系的显着转录变化相关,与生态失调所见的炎症特征相比,有一些共享的和一些不同的途径。这些结果强调了一种综合的、系统级的方法来理解宿主-微生物相互作用的重要性,同时对 FGT 粘膜复杂系统中的重要变量(如生殖激素)进行了评估。我们发现抗原呈递细胞 (APC) 是微生物组相关 FGT 炎症的关键介质。我们还发现 DMPA 与跨多个细胞谱系的显着转录变化相关,与生态失调所见的炎症特征相比,有一些共享的和一些不同的途径。这些结果强调了一种综合的、系统级的方法来理解宿主-微生物相互作用的重要性,同时对 FGT 粘膜复杂系统中的重要变量(如生殖激素)进行了评估。我们发现抗原呈递细胞 (APC) 是微生物组相关 FGT 炎症的关键介质。我们还发现 DMPA 与跨多个细胞谱系的显着转录变化相关,与生态失调所见的炎症特征相比,有一些共享的和一些不同的途径。这些结果强调了一种综合的、系统级的方法来理解宿主-微生物相互作用的重要性,同时对 FGT 粘膜复杂系统中的重要变量(如生殖激素)进行了评估。

更新日期:2021-09-16
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