Vertical transmission of Listeria monocytogenes

描述（由申请人提供）：胎儿-胎盘感染是妊娠并发症的主要原因，但对垂直传播的潜在分子和细胞机制知之甚少。已知引起胎儿-胎盘感染的微生物主要是细胞内病原体。其中之一是单核细胞增生李斯特菌，这是非常适合实验分析。我们建议使用L。单核细胞增多症作为模型细胞内病原体，以了解经胎盘传播的机制。我们已经开发了一种模仿人类疾病的妊娠豚鼠模型。在人类和豚鼠的胎盘中，单层滋养层将胎儿和母体循环分开。我们建议描述L.单核细胞增多症和滋养层细胞在体内，并确定胎儿胎盘感染所必需的病毒毒力因子。除了形成物理屏障外，滋养层被认为是对感染的先天免疫反应的一部分。我们建议分析滋养层细胞对L.单核细胞增多症的微阵列分析。了解经胎盘传播的机制将有助于设计更有效的治疗和疾病预防手段。 申请人是一名委员会认证的儿科医生，隶属于加州奥克兰儿童医院传染病科。她在儿科科学家发展计划的支持下启动了这个项目，并打算在这个应用程序的支持下继续她的研究。研究将在丹尼尔教授的实验室进行。他领导的一个实验室在建立L.单核细胞增生作为宿主-病原体相互作用的模型。拟议的研究将提供重要的培训，这将证明是至关重要的申请人，当她成为一个独立的医生科学家，她的长期目标。

DESCRIPTION (provided by applicant): Feto-placental infections represent a major cause for pregnancy complications, yet the underlying molecular and cellular mechanisms of vertical transmission are poorly understood. Organisms known to cause feto-placental infection are predominantly intracellular pathogens. Among those is Listeria monocytogenes, which is highly amenable to experimental analysis. We propose to use L. monocytogenes as a model intracellular pathogen to understand the mechanisms of transplacental transmission. We have developed a pregnant guinea pig model of listeriosis which mimics human disease. A single layer of trophoblasts separates fetal from maternal circulation in the placenta of humans and guinea pigs. We propose to characterize the interaction between L. monocytogenes and trophoblasts in vivo and to identify listerial virulence factors that are necessary for feto-placental infection. In addition to forming a physical barrier trophoblasts are thought to be part of the innate immune response to infection. We propose to analyze gene expression in trophoblasts in response to infection with L. monocytogenes by microarray analysis. Understanding the mechanisms of transplacental transmission will help in designing more effective means of treatment and disease prevention. The applicant is a board certified pediatrician and is affiliated with the Department of Infectious Diseases at Children's Hospital Oakland, CA. She has initiated this project with support from the Pediatric Scientist Development Program and intends to continue her studies with support from this application. The research will be conducted in the laboratory of Prof. Daniel A. Portnoy at UC Berkeley, who heads a laboratory that has been instrumental in establishing L. monocytogenes as a model for host-pathogen interactions. The proposed research will provide important training which will prove crucial for the applicant when she becomes an independent physician scientist, her long-term goal.