Role of Chlamydia Species in Preterm Birth and Placental Dysfunction

衣原体种类在早产和胎盘功能障碍中的作用

• 批准号: 8724108
• 负责人: Robin R Ingalls
• 金额: $ 5.38万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8724108
• 关键词: Accounting; Affect; Animals; Apoptosis; Bacteria; Bacterial Infections; Birth; Caring; Cessation of life; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Chronic; Clinical; Clinical Research; Congenital Abnormality; DNA; Data; Development; Environment; Etiology; Fetal Development; Fetal Growth Retardation; Fetus; Functional disorder; Gene Expression; Genital system; Gestational Age; Goals; Goat; Growth; Guidelines; Health; Histopathology; Hormonal Change; Human; Immune; Immune response; Immunohistochemistry; Immunologic Factors; Immunologic Receptors; Immunologics; Infant; Infection; Inflammation; Lead; Link; Maternal-Fetal Exchange; Modeling; Placenta; Play; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Premature Infant; Premature Labor; Public Health; Publishing; Reproductive Tract Infections; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Role; Ruminants; Secondary to; Sexually Transmitted Diseases; Sheep; Signal Pathway; Spontaneous abortion; Staging; Starvation; Survival Rate; T-Lymphocyte; Testing; Third Pregnancy Trimester; Tissues; Toll-Like Receptor 2; Tryptophan; Tryptophan 2,3 Dioxygenase; United States; Urine; Uterus; Virus Diseases; Woman; Work; abortion; adverse outcome; antimicrobial peptide; blind; chemokine; clinical care; cost; cytokine; fetal; improved; innovation; pathogen; receptor; receptor expression; response; screening; sensor; trophoblast

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.

描述（由申请人提供）：早产是一个重大的公共卫生问题，仅在美国每年就有超过 50 万的新生儿发生早产。 许多孕产妇状况已被认为是早产的危险因素，但对于大多数情况，其病因尚不完全清楚。 继发于感染或免疫因素的胎盘炎症被认为是早产的危险因素之一。 人们早就知道衣原体与反刍动物流产有关。 然而，沙眼衣原体是美国主要的细菌性传播感染 (STI)，也是世界上最流行的 STI 之一，它在女性不良妊娠结局中的作用仍存在争议。 许多因素，例如色氨酸饥饿，已被证明会促进持续的衣原体感染，其特征是活的、代谢活跃的细菌无法 划分。 巧合的是，胎盘是一种富含吲哚胺 2,3-双加氧酶 (IDO) 的组织，会导致细胞内色氨酸池的降解。 对于胎盘来说，这种现象可以抑制 T 细胞同种异体增殖反应，并且被认为发挥着重要作用。 母胎耐受性中的作用。 该 FOA 的目标是鼓励对影响胎盘功能的病原体进行新的和创新性的研究。 为此，我们开发了以下模型。 沙眼衣原体的下生殖道感染可以上升到胎盘水平，并且在一部分孕妇中，会发展成持续的形式，导致周围组织出现低度炎症。 我们假设胎盘被衣原体持续感染。可以引发或促进早产，并继发于这种慢性炎症损害胎儿发育，导致胎盘功能障碍、胎儿生长受限和早产。 这项工作的目标是：（1）表征胎盘的免疫框架及其对衣原体的反应能力~（2）确定胎盘组织衣原体感染导致慢性炎症和胎盘功能障碍的机制~ (3) 确定衣原体感染之间的临床关联。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危险因素，这可能会导致临床护理的变化并改善妊娠结局。