GBS mediated in utero fetal injury

描述(由申请人提供)：人类新生儿的发病率和死亡率是重大的公共卫生问题。新生儿发病率和死亡率的主要危险因素是侵袭性细菌感染和随之而来的严重炎症反应，这些反应主要始于子宫。B组链球菌(GBS)是导致早产、死产和早发性新生儿疾病的重要原因。促进GBS感染从下生殖道上升到胎儿的因素尚不清楚。我们的研究表明，毒力因子的上调促进了GBS在体外对胎盘膜的侵袭。使用人类胎盘膜和非人灵长类动物模型，这项提议的目标是从机械上定义毒力因子如何使宫内GBS感染和随后的胎儿肺和脑损伤上升。

DESCRIPTION (provided by applicant): Morbidity and mortality of human newborns are significant public health concerns. Predominant risk factors for neonatal morbidity and mortality are invasive bacterial infections and the ensuing severe inflammatory response, which mainly begin in utero. Group B Streptococci (GBS) are a significant cause of preterm births, stillbirths and early onset neonatal disease. Factors that facilitate ascending GBS infection from the lower genital tract to the fetus are not understood. Our studies indicate that upregulation of virulence factors facilitate GBS invasion of placental membranes in vitro. Using human placental membranes and a nonhuman primate model, the objective of this proposal is to mechanistically define how virulence factors enable ascending in utero GBS infection and subsequent fetal lung and brain injury.