Genetics of Host Resistance to Chlamydia trachomatis

宿主遗传变异在感染结局中起着很大的作用。因此，遗传分析是一种有效的方法 对传染病的抵抗力可以揭示影响疾病进程严重程度的重要基因。这 这种类型的基因分析已经在小鼠的各种感染模型中非常成功，而这一点 数据已经为可能影响人类感染的候选基因指明了方向。对于建议的遗传 实验中，我们决定将重点放在感染人类病原体衣原体的小鼠身上 沙眼衣原体。它是流行地区失明的主要原因，也可能是最常见的 世界上最大的细菌性传播疾病。基于对人类和动物的研究结果 感染衣原体，似乎至少会导致疾病症状的一些变化 从宿主易感性的遗传差异到衣原体疾病的不同因素。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 一种人类衣原体疾病。为了我们的第一个目标，我们将利用小鼠遗传学作为一种手段来提炼 数量性状基因座(QTL)的定位影响急性系统感染C. 沙眼衣原体，旨在模拟人类性传播疾病的元素，称为 性淋巴颗粒。对于第二个目标，我们将确定构成这些影响的基因 QTL。对于第三个目标，我们将研究在前两个目标中分离的基因，以确定它们对 细胞内细菌复制。 该项目将尝试定义影响小鼠感染霍乱病毒引起的疾病易感性的基因 沙眼衣原体。人类很可能会有相似的基因功能，从而影响相似的 对传染病的易感性。由于沙眼衣原体感染在人类中很常见 这些基因的知识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.