Gosmann Christina, Anahtar Melis N, Handley Scott A, Farcasanu Mara, Abu-Ali Galeb, Bowman Brittany A, Padavattan Nikita, Desai Chandni, Droit Lindsay, Moodley Amber, Dong Mary, Chen Yuezhou, Ismail Nasreen, Ndung'u Thumbi, Ghebremichael Musie S, Wesemann Duane R, Mitchell Caroline, Dong Krista L, Huttenhower Curtis, Walker Bruce D, Virgin Herbert W, Kwon Douglas S
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA; Harvard Medical School, Boston, MA 02115, USA.
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Immunity. 2017 Jan 17;46(1):29-37. doi: 10.1016/j.immuni.2016.12.013. Epub 2017 Jan 10.
Elevated inflammation in the female genital tract is associated with increased HIV risk. Cervicovaginal bacteria modulate genital inflammation; however, their role in HIV susceptibility has not been elucidated. In a prospective cohort of young, healthy South African women, we found that individuals with diverse genital bacterial communities dominated by anaerobes other than Gardnerella were at over 4-fold higher risk of acquiring HIV and had increased numbers of activated mucosal CD4 T cells compared to those with Lactobacillus crispatus-dominant communities. We identified specific bacterial taxa linked with reduced (L. crispatus) or elevated (Prevotella, Sneathia, and other anaerobes) inflammation and HIV infection and found that high-risk bacteria increased numbers of activated genital CD4 T cells in a murine model. Our results suggest that highly prevalent genital bacteria increase HIV risk by inducing mucosal HIV target cells. These findings might be leveraged to reduce HIV acquisition in women living in sub-Saharan Africa.
女性生殖道炎症水平升高与感染艾滋病毒的风险增加有关。宫颈阴道细菌可调节生殖器炎症;然而,它们在艾滋病毒易感性中的作用尚未阐明。在一项针对年轻、健康的南非女性的前瞻性队列研究中,我们发现,与以卷曲乳杆菌为主的菌群相比,生殖器细菌群落多样且以加德纳菌以外的厌氧菌为主的个体感染艾滋病毒的风险高出4倍多,且活化的黏膜CD4 T细胞数量增加。我们确定了与炎症减轻(卷曲乳杆菌)或炎症加剧(普雷沃菌属、斯尼氏菌属和其他厌氧菌)及艾滋病毒感染相关的特定细菌分类群,并发现高危细菌在小鼠模型中增加了活化的生殖器CD4 T细胞数量。我们的结果表明,高度普遍的生殖器细菌通过诱导黏膜艾滋病毒靶细胞来增加感染艾滋病毒的风险。这些发现可能有助于降低撒哈拉以南非洲地区女性感染艾滋病毒的几率。