Center for Global Health, Department of Medicine, Weill Cornell Medicine, New York, New York.
Genomics Resources Core Facility, Weill Cornell Medicine, New York, New York.
J Infect Dis. 2019 May 5;219(11):1777-1785. doi: 10.1093/infdis/jiy742.
Schistosomiasis increases the risk of human immunodeficiency virus (HIV) acquisition in women by mechanisms that are incompletely defined. Our objective was to determine how the cervical environment is impacted by Schistosoma haematobium or Schistosoma mansoni infection by quantifying gene expression in the cervical mucosa and cytokine levels in cervicovaginal lavage fluid.
We recruited women with and those without S. haematobium infection and women with and those without S. mansoni infection from separate villages in rural Tanzania with high prevalences of S. haematobium and S. mansoni, respectively. Infection status was determined by urine and stool microscopy and testing for serum circulating anodic antigen. RNA was extracted from cervical cytobrush samples for transcriptome analysis. Cytokine levels were measured by magnetic bead immunoassay.
In the village where S. haematobium was prevalent, 110 genes were differentially expressed in the cervical mucosa of 18 women with versus 39 without S. haematobium infection. Among the 27 cytokines analyzed in cervicovaginal lavage fluid from women in this village, the level of interleukin 15 was lower in the S. haematobium-infected group (62.8 vs 102.9 pg/mL; adjusted P = .0013). Differences were not observed in the S. mansoni-prevalent villages between 11 women with and 29 without S. mansoni infection.
We demonstrate altered cervical mucosal gene expression and lower interleukin 15 levels in women with S. haematobium infection as compared to those with S. mansoni infection, which may influence HIV acquisition and cancer risks. Studies to determine the effects of antischistosome treatment on these mucosal alterations are needed.
血吸虫病通过机制增加了女性获得人类免疫缺陷病毒(HIV)的风险,但这些机制尚未完全确定。我们的目的是通过定量宫颈黏膜基因表达和宫颈阴道灌洗液细胞因子水平,来确定曼氏血吸虫或埃及血吸虫感染如何影响宫颈环境。
我们分别从坦桑尼亚农村的两个村庄招募了患有和未患有埃及血吸虫感染的女性,以及患有和未患有曼氏血吸虫感染的女性。这些村庄的埃及血吸虫和曼氏血吸虫感染率分别较高。通过尿和粪便显微镜检查以及血清循环阳极抗原检测来确定感染状况。从宫颈细胞刷样本中提取 RNA 进行转录组分析。通过磁珠免疫测定法测量细胞因子水平。
在埃及血吸虫流行的村庄中,18 名患有埃及血吸虫感染的女性与 39 名未患有埃及血吸虫感染的女性的宫颈黏膜中有 110 个基因表达存在差异。在该村庄宫颈阴道灌洗液中分析的 27 种细胞因子中,白细胞介素 15 的水平在埃及血吸虫感染组中较低(62.8 与 102.9 pg/ml;调整后的 P =.0013)。在曼氏血吸虫流行的村庄中,11 名患有曼氏血吸虫感染的女性与 29 名未患有曼氏血吸虫感染的女性之间未观察到差异。
与感染曼氏血吸虫的女性相比,感染埃及血吸虫的女性宫颈黏膜基因表达发生改变,白细胞介素 15 水平降低,这可能影响 HIV 感染和癌症风险。需要研究抗血吸虫治疗对这些黏膜改变的影响。