Prodger Jessica L, Kaul Rupert
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA.
Department of Medicine, University of Toronto, Medical Sciences Building, Room #6356, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
AIDS Res Ther. 2017 Sep 12;14(1):49. doi: 10.1186/s12981-017-0167-6.
Circumcision reduces heterosexual HIV-1 acquisition in men by at least 60%. However, the biological mechanisms by which circumcision is protective remain incompletely understood. We test the hypothesis that the sub-preputial microenvironment created by the foreskin drives immune activation in adjacent foreskin tissues, facilitating HIV-1 infection through a combination of epithelial barrier disruption, enhanced dendritic cell maturation, and the recruitment/activation of neutrophils and susceptible CD4 T cell subsets such as Th17 cells. Furthermore, we provide evidence that the genital microbiome may be an important driver of this immune activation. This suggests that new modalities to reduce genital immune activation and/or alter the genital microbiome, used alone or in combination with topical microbicides, may be of significant benefit to HIV prevention.
包皮环切术可使男性异性传播感染HIV-1的几率至少降低60%。然而，包皮环切术具有保护作用的生物学机制仍未完全明确。我们检验了这样一个假设：包皮所形成的包皮下微环境会促使相邻包皮组织发生免疫激活，通过上皮屏障破坏、树突状细胞成熟增强以及中性粒细胞和易感CD4 T细胞亚群（如Th17细胞）的募集/激活等共同作用，促进HIV-1感染。此外，我们提供的证据表明，生殖微生物群可能是这种免疫激活的重要驱动因素。这表明，单独或与局部杀菌剂联合使用的、用于降低生殖器免疫激活和/或改变生殖微生物群的新方法，可能对预防HIV具有显著益处。
