Department of Global Health, University of Washington, Seattle, Washington, USA.
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA.
J Clin Invest. 2018 May 1;128(5):1985-1999. doi: 10.1172/JCI97043. Epub 2018 Apr 9.
Thirteen percent of pregnancies result in preterm birth or stillbirth, accounting for fifteen million preterm births and three and a half million deaths annually. A significant cause of these adverse pregnancy outcomes is in utero infection by vaginal microorganisms. To establish an in utero infection, vaginal microbes enter the uterus by ascending infection; however, the mechanisms by which this occurs are unknown. Using both in vitro and murine models of vaginal colonization and ascending infection, we demonstrate how a vaginal microbe, group B streptococcus (GBS), which is frequently associated with adverse pregnancy outcomes, uses vaginal exfoliation for ascending infection. GBS induces vaginal epithelial exfoliation by activation of integrin and β-catenin signaling. However, exfoliation did not diminish GBS vaginal colonization as reported for other vaginal microbes. Rather, vaginal exfoliation increased bacterial dissemination and ascending GBS infection, and abrogation of exfoliation reduced ascending infection and improved pregnancy outcomes. Thus, for some vaginal bacteria, exfoliation promotes ascending infection rather than preventing colonization. Our study provides insight into mechanisms of ascending infection by vaginal microbes.
13%的妊娠会导致早产或死产，每年造成 1500 万例早产和 350 万例死亡。这些不良妊娠结局的一个重要原因是阴道微生物引起的宫内感染。为了建立宫内感染，阴道微生物通过上行感染进入子宫；然而，其发生的机制尚不清楚。本研究通过阴道定植和上行感染的体外和小鼠模型，展示了一种与不良妊娠结局密切相关的阴道微生物——B 族链球菌（GBS）如何利用阴道脱落物进行上行感染。GBS 通过激活整合素和β-连环蛋白信号诱导阴道上皮脱落。然而，脱落并没有像其他阴道微生物那样减少 GBS 的阴道定植。相反，阴道脱落物增加了细菌的传播和上行 GBS 感染，而脱落物的减少则降低了上行感染并改善了妊娠结局。因此，对于某些阴道细菌而言，脱落物促进了上行感染，而不是防止了定植。本研究为阴道微生物上行感染的机制提供了新的见解。
