Genetics of Listeria induced changes in gene expression

描述（由申请人提供）：哺乳动物宿主，从近亲繁殖的小鼠菌株到人类，对各种细菌感染表现出广泛的表型反应。在小鼠中引起这种差异反应的病原体之一是单核细胞增生Listena，这是一种革兰氏阳性细菌，是食物中毒的常见来源。先前的研究已经证实，免疫反应的差异通常是由基因控制的。免疫反应的差异可以使用各种读数来表征，从基因表达变化到疾病结果。目前，基因表达数据是描述生物系统最全面的方法。此外，基因表达值可直接用于遗传数量性状作图实验。因此，通过监测对感染的差异转录反应，我们可以识别和表征控制感染的关键分子。为了实现这一目标，我们将在感染单核细胞增生李斯特菌后的差异易感近交系小鼠株中进行基因表达谱的全基因组表征。

DESCRIPTION (provided by applicant): Mammalian hosts, from inbred mouse strains to humans, display a wide range of phenotypic responses to various bacterial infections. One of the pathogens eliciting such differential responses in mice is Listena monocytogenes, a Gram-positive bacterium which is a common source of food poisoning. Previous studies have established that differences in immune response are often genetically controlled. Differences in immune response can be characterized using a variety of readouts, from gene expression changes to disease outcome. Currently, gene expression data is the most comprehensive way to describe a biological system. In addition, gene expression values can be used directly in genetic quantitative trait mapping experiments. Therefore, by monitoring differential transcriptional responses to infection, we can identify and characterize molecules critical for control of infection. To achieve this goal we will perform genome-wide characterization of gene expression profiles in differentially susceptible inbred mouse strains following infection with Listeria monocytogenes. To understand how changes in gene expression affect immune function, we have to differentiate between primary and secondary differences. Primary expression differences are caused by genetic polymorphisms at the gene locus itself, which directly affect the level of the gene transcript. Accordingly, secondary differences are those which reflect upstream functional or expression differences. We will use a novel Recombinant Inbred expression mapping approach to differentiate between primary and secondary changes in gene expression in mouse strains differentially susceptible to Listeria monocytogenes infection. Our pilot study will identify molecules differentially regulated in response to infection. Furthermore, it will allow us to refine our methodology for a future comprehensive study of changes in gene expression in differentially susceptible hosts over the course of the infectious disease. Identification of primary gene expression changes will lead to identification of genetic polymorphisms controlling gene expression. In addition, these primary expression differences will serve as starting points for building a multilayer map of transcriptional responses to infection. We hope to use this map to identify novel therapeutic targets for treatment of infectious diseases.