Innate Immune Responses of Trophoblasts in Pregnancy

妊娠期滋养层细胞的先天免疫反应

• 批准号: 7390377
• 负责人: Vikki M Abrahams
• 金额: $ 26万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7390377
• 关键词: Allogenic; Animal Model; Apoptosis; Apoptotic; Area; Caspase; Cell Differentiation process; Cell physiology; Cells; Complex; Condition; Conserved Sequence; Data; Effector Cell; Endometrium; Fetal Growth Retardation; Fetus; First Pregnancy Trimester; Host Defense; Human; Immune response; Immune system; Infection; Inflammatory; Ligation; Link; Maternal-Fetal Exchange; Mediating; Molecular; Mus; Mutate; Pathway interactions; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Premature Labor; Process; Production; Proteins; Rate; Receptor Activation; Regulation; Research Personnel; Role; Signal Transduction; Site; Surface; Syncytiotrophoblast; Testing; Thinking; Toll-Like Receptor 1; Toll-Like Receptor 2; Toll-like receptor 6; Toll-like receptors; adapter protein; cytokine; cytotrophoblast; fetal; immune function; in vivo; insight; microbial; microorganism; novel; pathogen; programs; receptor expression; response; toll-like receptor 4; trophoblast

DESCRIPTION (provided by applicant): The relationship between intrauterine infections and complications of pregnancy is poorly understood. Our central hypothesis is that first trimester trophoblast cells can recognize and respond to pathogens through Toll-like receptors, and that such innate immune functions of trophoblast cells may influence pregnancy outcome. Toll-like receptors (TLR) are key components of the innate immune system which recognize conserved sequences on the surface of microorganisms and trigger effector cell functions via the signaling adapter protein, MyD88. We have demonstrated that first trimester trophoblast cells express TLR-2 and TLR-4. Following ligation by gram-positive bacterial components, TLR-2 mediates apoptosis in first trimester trophoblast cells. In contrast, ligation of TLR-4 by gram-negative bacterial components induces cytokine production. Thus, we have found that trophoblast cells can mount divergent responses to different bacterial components through two distinct TLR. Our objectives are to further characterize the mechanisms by which TLR-2 and TLR-4 function in first trimester trophoblast cells and to determine their role during pregnancy. Our specific aims are to: 1. Determine the mechanisms by which TLR-2 functions in first trimester trophoblast cells 2. Determine the mechanism by which TLR-4 functions in first trimester trophoblast cells 3. Determine the regulation of TLR expression by first trimester trophoblast cells 4. Determine the effects of TLR activation on pregnancy in vivo Little is known about how trophoblast cells recognize and respond to microorganisms. The area of Toll-like receptors in pregnancy is a novel one. Therefore, it is important to understand the role of Toll-like receptors within the normal placenta. These studies will provide new insight into how trophoblast cells function in the presence of an infection and will advance our understanding of pathological conditions, such as preeclampsia, IUGR or preterm deliveries.

描述（由申请人提供）：对宫内感染与怀孕并发症之间的关系知之甚少。我们的中心假设是，一个三个月的滋养细胞可以通过Toll样受体识别并应对病原体，并且这种滋养细胞细胞的这种先天免疫功能可能会影响妊娠结局。 Toll样受体（TLR）是先天免疫系统的关键组成部分，它通过信号衔接蛋白MyD88识别微生物表面上的保守序列和触发效应细胞功能。我们已经证明了头三个月滋养细胞表达TLR-2和TLR-4。革兰氏阳性细菌成分结扎后，TLR-2介导了三个月滋养细胞细胞的凋亡。相比之下，革兰氏阴性细菌成分通过革兰氏阴性成分结扎诱导细胞因子的产生。因此，我们发现，滋养细胞可以通过两个不同的TLR对不同细菌成分产生不同的反应。我们的目标是进一步表征TLR-2和TLR-4在妊娠中期滋养细胞细胞中发挥作用的机制，并确定其在怀孕期间的作用。 我们的具体目的是： 1。确定TLR-2在三个月滋养细胞中发挥作用的机制 2。确定TLR-4在三个月滋养细胞中起作用的机制 3。确定第一个三个月滋养细胞对TLR表达的调节 4。确定TLR激活对体内妊娠的影响 关于滋养细胞如何识别和对微生物的反应知之甚少。怀孕期间的收费受体面积是新颖的。因此，重要的是要了解正常胎盘中的Toll样受体的作用。这些研究将提供有关滋养细胞在感染存在下如何发挥作用的新见解，并将提高我们对病理状况的理解，例如先兆子痫，IUGR或早产。