Genetic analysis of mechanisms of chlamydial immune evasion

摘要 沙眼衣原体性传播感染率稳定或增加，这些感染 每年在全世界造成数十亿的医疗费用。这些病原体的疫苗是必要的，但我们有限的 了解衣原体如何逃避免疫系统并靶向宿主的不同组织， 阻碍了这一目标的实现。规避宿主的菌株和物种特异性衣原体基因 干扰素刺激防御，以及其他干扰素非依赖性基因，介导这些生物体的能力 侵袭不同的组织，可能与C.沙眼衣原体 分离株然而，这些基因中的大多数还没有被鉴定，因为基因操作的方法， 这些病原体只是最近才开发出来的。在我们的研究目标之一，我们将使用正向遗传算法， 屏幕，新的遗传作图工具和小鼠模型，以确定基因，小鼠适应C。沙眼衣原体 相关用途，以逃避免疫和感染不同组织的小鼠和解剖这些功能如何。类似 方法将用于目标2中，以识别和表征C.沙眼基因， 介导这些生物体附着、侵入和避免不同人类中的免疫应答的能力。 组织中最后，在目标3中，我们将开发新的衣原体遗传学方法，使其更容易识别， 并检验有关基因功能的假设，这些基因调节这些生物体入侵的能力， 不同的组织，逃避宿主的免疫反应。

Abstract Rates of Chlamydia trachomatis sexually transmitted infection are stable or increasing and these infections incur billions in medical costs annually worldwide. Vaccines for these pathogens are needed but our limited understanding of how chlamydiae evade the immune system and target different tissues of their hosts has hindered progress towards this goal. Strain- and species-specific Chlamydia genes that circumvent host interferon stimulated defenses, and other interferon independent genes that mediate ability of these organisms to invade different tissues, may be linked to differences in the pathogenesis of closely-related C. trachomatis isolates. However, most of these genes have not been identified because methods for genetic manipulation of these pathogens have only been recently developed. In aim one of our study we will use forward genetic screens, new genetic mapping tools and mouse models to identify genes that a mouse-adapted C. trachomatis relative uses to evade immunity and infect different tissues in mice and dissect how these function. Similar approaches will be used in aim 2 to identify and characterize the functions of C. trachomatis genes that mediate the ability of these organisms to attach to, invade and avoid immune responses in distinct human tissues. Finally, in aim 3 we will develop new genetic approaches for Chlamydia that make it easier to identify, and test hypothesis concerning the functions of the genes that mediate abilities of these organisms to invade different tissue and evade immune responses of their hosts.