Genetic control of immune response to Listeria infection

尽管公共卫生稳步改善，但从集中化的食品制造到 潜在的生物恐怖主义使接触食源性病原体的风险很高。在人类人口中， 对感染的免疫反应的差异是由它们各自独特的等位基因组合决定的。 个人的。我们的长期目标是了解免疫功能的变异程度，并确定 这种变异如何影响感染的过程和结果。 单核细胞增生性李斯特菌是一种革兰氏阳性细菌，既是人类重要的病原体，也是一种 经过验证的研究免疫功能的工具。然而，很难研究对L. 人类人群中的单核细胞增多性感染。另一方面，近亲繁殖的小鼠品系是遗传的。 对L单核细胞增多症感染表现出广泛的敏感性。对于我们的研究 单核细胞增多性李斯特菌易感性的遗传控制，我们选择了敏感的BALB/cByJ和 耐药，C57BL/6ByJ，小鼠品系。我们对这些菌株F2代存活率的分析 静脉感染L单核细胞增多症患者发现两个主效数量性状基因座 我们目前的目标是对这些基因进行定位克隆 控制这些基因座对L单核细胞增多症感染的差异反应。要做到这一点 我们会： 1.对单核细胞增多性李斯特菌易感基因座进行精细定位。我们将进行广泛的遗传和表型研究 检查我们的同源小鼠品系，减少基因座的大小并确定它们的边界。 2.确定可能控制单核细胞增多性李斯特菌的候选基因 对单核细胞增多性李斯特菌感染的不同敏感性将通过定位克隆相结合的方法进行鉴定。 和一个假设驱动的策略 3.确定多态基因在控制单核细胞增多性李斯特菌感染中的作用。我们将建立 CXCL11在转基因控制L单核细胞增多症感染中的决定性作用。在……里面 此外，我们将创建分析其他候选人的框架。

Despite steady improvements in public health, factors ranging from centralized food manufacturing to potential bioterrorism keep the risk of exposure to foodborne pathogens high. In the human population, differences in immune response to infection are determined by the unique allelic combinations of each individual. Our long term goal is to understand the extent of variation in immune function and to determine how this variation affects the course and outcome of infection. Listeria monocytogenes is a gram positive bacterium which is both an important human pathogen and a proven tool to study immune function. It is however difficult to study the genetic control of sensitivity to L. monocytogenes infection in human populations. Inbred strains of mice, on the other hand, are genetically tractable and display a wide range of sensitivities to L monocytogenes infection. For our studies of the genetic control of susceptibility to L. monocytogenes infection, we selected the sensitive, BALB/cByJ, and resistant, C57BL/6ByJ, strains of mice. Our analysis of the survival of F2 progeny of these strains following intravenous infection with L monocytogenes identified two major quantitative trait loci (QTLs), Listrl on chromosome 5 and Listr2 on chromosome 13. Our current goal is to perform positional cloning of the genes controlling the differential response to L monocytogenes infection contained in these loci. To achieve this we will: 1. Fine map the L. monocytogenes susceptibility loci. Wewill perform extensive genetic and phenotypic examination of our congenic mouse lines, decrease the size of the loci and define their boundaries. 2. Identify candidate L. monocytogenes sensitivity genes Polymorphic genes that are likely to control differential sensitivity to L. monocytogenes infection will be identified by a combination of a positional cloning and a hypothesis driven strategies 3. Establish the role of polymorphic genes in control of L. monocytogenes infection. Wewill establish the definitive role of CXCL11 in control of L monocytogenes infection using transgenic approaches. In addition we will create the framework for analysis of additional candidates.