Pathways of Maternal Anemia

项目摘要 妊娠期疟疾是热带国家的一个严重公共卫生问题， 母亲和孩子的疾病和死亡率疟疾引起的妊娠晚期炎症反应 女性（患有这种疾病）。胎盘中高水平的TNF-α与母体贫血有关 但在多次妊娠中没有。我们假设，促炎信号通路， 早孕妇女改变胎盘中红细胞生成特异性因子的表达，导致贫血 通过以下途径之一或两者。1.炎症细胞因子和其他巨噬细胞介质 抑制调节红细胞生成的胎盘因子的表达。2.胎盘寄生虫粘连 合体滋养层直接调节调节红细胞生成的胎盘因子的表达。 蛋白质组学研究构成了一个无偏见的方法来调查全球蛋白质表达的差异。 在这里，我们将检查胎盘血浆蛋白质组的变化，与疟疾贫血途径的网站， 寄生虫隔离和炎症-胎盘。具体而言，研究将研究1。变化 胎盘血浆蛋白质组与疟疾贫血的关系2. 胎盘免疫细胞分泌组的定量蛋白质组学研究。3.证实疟疾 贫血途径蛋白与坦桑尼亚妇女群体中的疟疾贫血有关。基于这些 我们预期的假设是，转录因子、生长因子和 胎盘血中与红细胞生成相关的免疫调节剂将与母体血红蛋白相关 程度.我们预期调节红系细胞增殖和发育的巨噬细胞特异性介质 在孕妇的胎盘血液样本中含量更高。 妊娠期疟疾是最为人所知的疟疾综合征。血浆蛋白质组的特征 感染疟疾的孕妇将有助于我们了解在疟疾发病过程中宿主-病原体的相互作用。 怀孕的宿主，并将产生信息，为更大的研究新的分子参与发病机制 严重贫血的儿童。项目叙述 在疟疾流行地区，妊娠期疟疾是孕产妇因贫血而死亡的一个危险因素。妊娠 疟疾和母亲贫血是低出生体重分娩的独立危险因素， 新生儿期和婴儿期的死亡风险。这项研究将确定潜在的免疫和 转录途径和介质是关键的发病机制疟疾相关的孕产妇 贫血

Project Summary Pregnancy malaria is an overwhelming public health problem in tropical countries, which has been related to disease and mortality for both the mother and her child. Malaria induces inflammatory responses in primigravid women (who suffer from the disease). High TNF-¿ levels in the placenta are associated with maternal anemia in primigravidas but not in multigravidas. We hypothesize that proinflammatory signaling pathways in primigravid women modify the expression of erythropoiesis-specific factors in the placenta, leading to anemia through one or both of the following pathways. 1. Inflammatory cytokines and other macrophage mediators suppress the expression of placental factors that regulate erythropoiesis. 2. Parasite adhesion to placental syncytiotrophoblast directly modulates the expression of placental factors that regulate erythropoiesis. Proteomics studies constitute a nonbiased approach to investigate differences in global protein expression. Here we will examine placental plasma proteome changes related to malarial anemia pathway at the site of parasite sequestration and inflammation-the placenta. Specifically, the study will examine 1. Changes in placental plasma proteome associated with malarial anemia by using quantitative proteomics tools. 2. Characterize the secretome of placental immune cells by quantitative proteomics. 3. Confirm that malaria anemia pathway proteins are associated with malaria anemia in cohorts of Tanzanian women. Based on these hypotheses we expect, that the relative abundance of transcription factors, growth factors and immunomodulators in placental blood associated with erythropoiesis will correlate with maternal hemoglobin levels. We expect that macrophage-specific mediators that modify erythroid proliferation and development will be more abundant in placental blood samples from primigravidas. Pregnancy malaria is the best-understood malaria syndrome. The characterization of the plasma proteome in malaria-infected pregnant women will contribute to our understanding of the host-pathogen interaction in the pregnant host, and will generate information for larger studies of novel molecules involved in the pathogenesis of severe anemia in children. Project Narrative In malaria endemic areas, pregnancy malaria is a risk factor for maternal mortality due to anemia. Pregnancy malaria and maternal anemia are independent risk factors for low birth weight (LBW) deliveries that increase the risk of mortality during the neonatal period and infancy. This study will identify potential immunological and transcriptional pathways and mediators that are pivotal in the pathogenesis of malaria associated maternal anemia.