Role of Chlamydia Species in Preterm Birth and Placental Dysfunction

描述（由申请人提供）：早产是一个主要的公共卫生问题，仅在美国每年就有50多万例出生。 一些母体条件已被认为是早产的危险因素，但对于大多数情况下，病因并不完全清楚。 感染或免疫因素引起的胎盘炎症被认为是早产的危险因素之一。 长期以来，人们一直认为衣原体与反刍动物的流产有关。 然而，C.沙眼是美国最主要的细菌性传播感染（STI），也是世界上最流行的STI之一，其对妇女不良妊娠结局的影响仍有争议。 许多因素，如色氨酸饥饿，已被证明是促进持续性衣原体感染，其特征是活的，代谢活跃的细菌， 分开 巧合的是，胎盘是吲哚胺2，3-双加氧酶（IDO）高的组织，其导致色氨酸的细胞内池的降解。 对于胎盘来说，这种现象起到抑制T细胞同种异体增殖反应的作用，并且被认为在胎盘中起重要作用。 在母胎耐受中的作用。 该FOA的目标是鼓励对影响胎盘功能的病原体进行新的创新研究。 为此，我们开发了以下模型。 下生殖道感染C.沙眼可以上升到胎盘的水平，并且在孕妇的一个子集中，发展成可以在周围组织中驱动低度炎症的持久形式。 我们推测胎盘持续感染衣原体。可引发或促进早产并损害继发于这种慢性炎症的胎儿发育，导致胎盘功能障碍、胎儿生长受限和早产。 本研究的目的是：（1）了解胎盘的免疫结构及其对衣原体的免疫应答能力。(2)确定胎盘组织衣原体感染可导致慢性炎症和胎盘功能障碍的机制;（3）确定衣原体感染与胎盘功能障碍的临床相关性。和不良妊娠结局。 我们相信，我们的数据将确定早产的可治疗风险因素，这可能导致临床护理的变化，改善妊娠结局。

DESCRIPTION (provided by applicant): Preterm birth is a major public health problem, occurring in more than half a million births per year in the US alone. A number of maternal conditions have been recognized as risk factors for preterm birth, but for the majority of cases, the etiology is not completely understood. Placental inflammation secondary to infectious or immunologic factors is believed to be one of the risk factors for preterm labor. Chlamydia species have long been known to be associated with abortion in ruminants. However, the role of C. trachomatis, the leading bacterial sexually transmitted infection (STI) in the United States and one of the most prevalent STIs in the world, in adverse pregnancy outcome in women is still debated. A number of factors, such as tryptophan starvation, have been shown to promote persistent Chlamydia infection, characterized by viable, metabolically active bacteria that fail to divide. Coincidentally, the placenta is a tissue high in indoleamine 2,3-dioxygenase (IDO), which results in the degradation of intracellular pools of tryptophan. For the placenta, this phenomenon serves to inhibit T-cell alloproliferative responses and it is felt to play an important role in maternal-fetal tolerance. The goal of this FOA is to encourage new and innovative studies of pathogens that affect placental function. To that end, we have developed the following model. Lower reproductive tract infection with C. trachomatis can ascend to the level of the placenta, and in a subset of pregnant women, develop into a persistent form that can drive low grade inflammation in the surrounding tissue. We hypothesize that persistent infection of the placenta with Chlamydia spp. can trigger or promote preterm birth and impair fetal development secondary to this chronic inflammation, leading to placental dysfunction, growth restriction of the fetus, and preterm birth. The goal of this work is to: (1) Characterize the immunologic framework of the placenta and its ability to respond to Chlamydia spp.~ (2) Determine the mechanism by which Chlamydia infection of placental tissue can lead to chronic inflammation and placental dysfunction~ and (3) Determine the clinical association between infection with Chlamydia spp. and adverse pregnancy outcomes. We believe that our data will identify a treatable risk factor for preterm labor, which could lead to changes in clinical care an improved pregnancy outcomes.