Mechanisms mediating adverse birth outcomes in the context of S. Japonicum infect

描述（由申请人提供）：本K02的广泛目标是扩大我们对日本血吸虫感染背景下介导不良出生结果的基本机制的理解，并扩展已建立的研究者的科学专业知识领域。拟议的工作将利用由NIH资助的吡喹酮治疗妊娠期日本血吸虫的随机对照试验（U01AI066050）收集的基础设施和样本。U01的研究刚刚开始了5年来的第二个阶段，将于2007年6月中旬开始招募。这项工作的具体目标是研究日本血吸虫治疗如何改变胎盘铁代谢，改变胎盘细胞因子微环境，以及这如何改变胎盘健康，通过滋养细胞凋亡的定量定义。这项工作在本质上是高度协作的，允许检查日本血吸虫相关妊娠发病率的基本机制，而不是U01研究。这将使首席研究员能够探索新的研究途径，这不是她目前的主要技能。日本血吸虫为理解系统性炎症（包括炎症性贫血及伴随的铁代谢改变）如何影响妊娠结局提供了一个杰出的模型。由于它很容易治疗，全身性炎症在治疗几周内就会消失，因此这种疾病为研究怀孕期间全身性炎症的影响提供了一个很好的模型。因此，这项工作可以推广到许多传染性和非传染性的妊娠疾病，这些疾病会产生旺盛的促炎免疫反应，包括艾滋病毒、结核病、系统性红斑狼疮等。

DESCRIPTION (provided by applicant): The broad goals of this K02 are to expand our understanding of basic mechanisms mediating adverse birth outcomes in the context of S. japonicum infection and to extend the areas of scientific expertise of an established investigator. The proposed work will leverage the infrastructure and samples collected by an NIH funded randomized controlled trial (U01AI066050) of praziquantel treatment for S. japonicum during pregnancy. The U01 study just started its second of five years and will begin recruitment in mid June of 2007. The specific goals of this work are to examine how treatment for S. japonicum alters placental iron metabolism, modifies the cytokine micro-environment of the placenta, and how this alters placental health as defined by quantification of trophoblast apoptosis. This work is highly collaborative in nature, allowing examination of basic mechanism of S. japonicum related pregnancy morbidity not addressed by the U01 study. This will allow the principal investigator to explore novel avenues of inquiry, not currently her primary skill set. S. japonicum offers an outstanding model for understanding how systemic inflammation, including anemia of inflammation with attendant alterations in iron metabolism affects pregnancy outcomes. Due to the fact that it is easily treated and systemic inflammation is shown to dissipate within a few weeks of therapy, this disease provides an excellent model in which to study the effects of systemic inflammation during pregnancy. Thus, this work is generalizable to a host of infectious and non-infectious diseases of pregnancy that generate an exuberant pro-inflammatory immune response including HIV, tuberculosis, systemic lupus erythematosus, and many others.