Anahtar Melis N, Byrne Elizabeth H, Doherty Kathleen E, Bowman Brittany A, Yamamoto Hidemi S, Soumillon Magali, Padavattan Nikita, Ismail Nasreen, Moodley Amber, Sabatini Mary E, Ghebremichael Musie S, Nusbaum Chad, Huttenhower Curtis, Virgin Herbert W, Ndung'u Thumbi, Dong Krista L, Walker Bruce D, Fichorova Raina N, Kwon Douglas S
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA; Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA.
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, MA 02139, USA.
Immunity. 2015 May 19;42(5):965-76. doi: 10.1016/j.immuni.2015.04.019.
Colonization by Lactobacillus in the female genital tract is thought to be critical for maintaining genital health. However, little is known about how genital microbiota influence host immune function and modulate disease susceptibility. We studied a cohort of asymptomatic young South African women and found that the majority of participants had genital communities with low Lactobacillus abundance and high ecological diversity. High-diversity communities strongly correlated with genital pro-inflammatory cytokine concentrations in both cross-sectional and longitudinal analyses. Transcriptional profiling suggested that genital antigen-presenting cells sense gram-negative bacterial products in situ via Toll-like receptor 4 signaling, contributing to genital inflammation through activation of the NF-κB signaling pathway and recruitment of lymphocytes by chemokine production. Our study proposes a mechanism by which cervicovaginal microbiota impact genital inflammation and thereby might affect a woman's reproductive health, including her risk of acquiring HIV.
乳酸杆菌在女性生殖道中的定殖被认为对维持生殖健康至关重要。然而,关于生殖微生物群如何影响宿主免疫功能并调节疾病易感性,我们所知甚少。我们对一组无症状的南非年轻女性进行了研究,发现大多数参与者的生殖群落中乳酸杆菌丰度较低且生态多样性较高。在横断面和纵向分析中,高多样性群落与生殖促炎细胞因子浓度密切相关。转录谱分析表明,生殖抗原呈递细胞通过Toll样受体4信号通路原位感知革兰氏阴性菌产物,通过激活NF-κB信号通路和趋化因子产生募集淋巴细胞,从而导致生殖炎症。我们的研究提出了一种机制,通过该机制宫颈阴道微生物群影响生殖炎症,进而可能影响女性的生殖健康,包括感染HIV的风险。