Role of Chlamydia Species in Preterm Birth and Placental Dysfunction

描述(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多万新生儿出生。许多母亲的状况已经被认为是早产的危险因素，但对于大多数病例来说，病因并不完全清楚。感染或免疫因素继发的胎盘炎症被认为是早产的危险因素之一。长期以来，人们一直知道衣原体与反刍动物的流产有关。然而，沙眼衣原体是美国最主要的细菌性性传播感染(STI)，也是世界上最流行的性传播感染之一，其在女性不良妊娠结局中的作用仍存在争议。许多因素，如色氨酸饥饿，已被证明促进了衣原体的持续感染，其特征是活的、代谢活跃的细菌无法 分头行动。巧合的是，胎盘是一种高吲哚胺2，3-双加氧酶(IDO)的组织，它会导致细胞内色氨酸的降解。对于胎盘来说，这一现象抑制了T细胞的同种增殖反应，并被认为起到了重要的作用 在母胎耐受性中的作用。FOA的目标是鼓励对影响胎盘功能的病原体进行新的和创新的研究。为此，我们开发了以下模型。下生殖道感染沙眼衣原体可以上升到胎盘水平，在一小部分孕妇中，会发展成一种持续性的形式，可以在周围组织中引发低度炎症。我们假设胎盘持续感染衣原体。可引发或促进早产，损害胎儿发育，继发于这种慢性炎症，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)鉴定胎盘的免疫结构及其对衣原体的应答能力。~(2)确定衣原体感染导致胎盘慢性炎症和胎盘功能障碍的机制。(3)确定衣原体感染与临床的相关性。和不良妊娠结局。我们相信，我们的数据将确定早产的一个可治疗的危险因素，这可能会导致临床护理的变化和改善妊娠结局。 与公共健康相关：美国每年有超过50万名婴儿早产。虽然这些婴儿的存活率有所提高，但许多人仍然存在长期的健康问题。大多数早产病例都无法解释，但人们认为子宫内的感染可能起到了一定作用。我们想要确定被称为衣原体的常见性病是否在婴儿的早产中起作用。如果是这样，那么改变孕妇对这种感染的筛查和治疗可能会减少早产儿的数量。

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. PUBLIC HEALTH RELEVANCE: More than half a million babies are born prematurely each year in the U.S. While survival rates for these babies have improved, many remain with long-term health problems. Most cases of premature delivery are unexplained, but it is believed that infection in the womb may play a role. We want to determine if the common venereal disease known as Chlamydia plays any role in early delivery of babies. If so, then changes in screening and treatment of pregnant women for this infection could decrease the number of premature babies.