Genetic analysis of mechanisms of chlamydial immune evasion

摘要 沙眼衣原体性传播感染率稳定或上升，这些感染引起 全球每年数十亿美元的医疗费用。针对这些病原体的疫苗是必要的，但我们的有限 了解衣原体如何逃避免疫系统并以宿主不同组织为靶标 阻碍了实现这一目标的进展。绕过宿主的菌株和物种特异性衣原体基因 干扰素刺激防御，以及其他不依赖干扰素的基因，调节这些生物体的能力 侵袭不同的组织，可能与密切相关的沙眼衣原体的发病机制不同有关 分离株。然而，这些基因中的大多数还没有被识别出来，因为基因操作的方法 这些病原体是最近才开发出来的。在我们的一项研究中，我们将使用正向基因筛查， 新的遗传作图工具和小鼠模型用于识别小鼠适应的沙眼衣原体相关基因 用来逃避免疫和感染小鼠的不同组织，并剖析这些组织是如何发挥作用的。类似的方法 将在目标2中用于鉴定和表征沙眼衣原体基因的功能，这些基因介导了 这些生物附着、入侵和避免来自不同人类的代表性细胞的免疫反应 纸巾。

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 Chlamydia species 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 representative cells from different human tissues.