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: 8355427
• 负责人: Robin R Ingalls
• 金额: $ 56.81万
• 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/8355427
• 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; Screening procedure; 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; 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. 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.

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500万人出生。 许多产妇条件已被认为是早产的危险因素，但是在大多数情况下，病因尚未完全理解。 继发于传染性或免疫学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，众所周知，衣原体与反刍动物的流产有关。 然而，在美国，领先的细菌性传播感染（STI）和世界上最普遍的性传播性传播感染（STI）的作用在女性的不良怀孕结果中仍在争论。 许多因素（例如色氨酸饥饿）已被证明会促进持续性衣原体感染，其特征是可行的，代谢活性的细菌 划分。 巧合的是，胎盘是吲哚胺2,3-二氧酶（IDO）中高的组织，导致色氨酸的细胞内池降解。 对于胎盘，这种现象有助于抑制T细胞同种相化反应，并且认为它发挥了重要的作用 在母亲耐受性中的作用。 该FOA的目的是鼓励对影响胎盘功能的病原体的新创新研究。 为此，我们开发了以下模型。 较低的生殖道感染了沙眼梭状芽孢杆菌可以上升到胎盘的水平，在孕妇的一部分中，会发展成一种持续形式，可以驱动周围组织中的低年级炎症。 我们假设胎盘与衣原体属的持续感染。可以触发或促进早产，并损害这种慢性炎症继发的胎儿发育，从而导致胎盘功能障碍，胎儿的生长限制和早产。 这项工作的目的是：（1）表征胎盘的免疫学框架及其对衣原体的反应能力。和不良怀孕结果。 我们认为，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，从而改善了妊娠结局。 公共卫生相关性：在美国，每年有超过半百万的婴儿在美国过早出生，而这些婴儿的生存率有所提高，许多婴儿仍然存在长期健康问题。 大多数过早分娩的情况都无法解释，但是据信，子宫感染可能起作用。 我们要确定称为衣原体的常见性疾病是否在婴儿早期分娩中起任何作用。 如果是这样，那么对这种感染的孕妇的筛查和治疗变化可能会减少早产婴儿的数量。