Genetics of Host Resistance to Chlamydia trachomatis

宿主的遗传变异在感染的结果中起着很大的作用。因此，遗传分析 对传染病的抵抗力可以揭示影响疾病进程严重性的重要基因。这 这种类型的遗传分析在小鼠的各种感染模型中非常成功， 数据已经为可能影响人类感染的候选基因指明了方向。对于拟议的遗传 实验中，我们决定把重点放在小鼠感染人类病原体衣原体 沙眼它是流行地区致盲的主要原因，也可能是最常见的致盲源。 细菌性性传播疾病根据人类和动物的研究结果， 衣原体感染，似乎至少有一些疾病症状的变化导致 从宿主易感性的遗传差异到衣原体疾病的不同元素。因此，我们希望 为了研究宿主遗传背景在衣原体感染严重程度中的作用，使用小鼠模型， 一种人类衣原体疾病对于我们的第一个目标，我们将利用小鼠遗传学作为一种手段来完善 定位影响急性全身感染C. 沙眼，它被设计用来模拟人类性传播疾病的元素， 性病淋巴肉芽肿对于第二个目标，我们将确定这些影响的基础基因， QTL。对于第三个目标，我们将研究前两个目标中分离的基因，以确定它们对 细胞内细菌复制。 该项目将试图确定小鼠基因，这些基因影响对由感染引起的疾病的易感性。 沙眼衣原体。人类很可能会有类似的基因功能， 对传染病的易感性。由于沙眼衣原体感染在人类中很常见， 因此，了解这些基因可能有助于设计诊断或治疗方法。 感染

Host genetic variation plays a large role in the outcome of infection. Therefore, genetic analysis of resistance to infectious disease can reveal genes important for affecting the severity of disease course. This type of genetic analysis has been very successful in the mouse for a variety of infection models, and this data has pointed the way to candidate genes that could affect human infections. For the proposed genetic experiments, we have decided to focus on mouse infections with the human pathogen Chlamydia trachomatis. It is a major cause of blindness in endemic regions, and may be the most common source of bacterial sexually transmitted disease in the world. Based on the results of studies of human and animal infections with Chlamydia, it seems likely that at least some of the variations in disease symptoms result from genetic differences in host susceptibility to distinct elements of chlamydial disease. Therefore, we want to study the role of host genetic background in the severity of Chlamydia infections, using a mouse models of a human chlamydial disease. For our first Aim, we will utilize mouse genetics as a means to refine the location of Quantitative Trait Loci (QTL) that influence the outcome of an acute systemic infection with C. trachomatis, which is designed to model elements of the human sexually transmitted disease called lymphogranulum venereum. For the second Aim, we will identify the genes that underlie the effects of those QTL. For the third Aim, we will study the genes isolated in the first 2 Aims, to determine their effects on intracellular bacterial replication. This project will attempt to define mouse genes that affect susceptibility to disease caused by infections with Chlamydia trachomatis. It is likely that humans will have similar gene functions that will influence similar susceptibilities to infectious disease. Since infections with Chlamydia trachomatis are common in the human population, it is possible that knowledge of these genes could help to design diagnostics or therapies for this infection.