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Genetic analysis of mechanisms of chlamydial immune evasion

衣原体免疫逃避机制的遗传分析

基本信息

批准号：
10374061
负责人：
David Emmet Nelson
金额：
$ 56.02万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-02-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10374061
关键词：
Antibiotics Attenuated Bacteria Blindness Cells Cervix Uteri Chlamydia Chlamydia Infections Chlamydia muridarum Chlamydia trachomatis Chromosome Mapping Data Disease Ectopic Pregnancy Epithelial Epithelial Cells Fibroblasts Funding Gastrointestinal tract structure Genes Genetic Genetic Recombination Genetic Screening Genitourinary system Genome Goals HIV Human Immune Immune Evasion Immune Targeting Immune response Immune system Immunity In Vitro Infection Interferon Type II Interferons Invaded Lead Link Lymphatic System Lymphogranuloma Venereum Mammalian Oviducts Maps Mediating Medical Care Costs Methods Modeling Molecular Mus Nucleotides Organism Organism Strains Pathogenesis Pathogenicity Pelvic Inflammatory Disease Peripheral Phenotype Radiation Resistance Rodent Sexual Transmission Sexually Transmitted Diseases Syndrome Time Tissues Trachoma Triad Acrylic Resin Tropism Urethra Urethritis Vaccine Design Vaccines Virulence Factors Woman adaptive immunity clinically relevant conjunctiva cytokine epidemiologic data experimental study gastrointestinal epithelium genetic analysis genetic manipulation human disease human female human pathogen human tissue insight male men mouse model mutant novel novel vaccines pathogen prevent rectal reproductive tract standard of care tissue tropism tool transmission process urogenital tract

项目摘要

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.

抽象的沙眼衣原体性传播感染率稳定或上升，并且这些感染会导致全球每年的医疗费用达数十亿美元。需要针对这些病原体的疫苗，但我们的能力有限了解衣原体物种如何逃避免疫系统并针对宿主的不同组织阻碍了实现这一目标的进展。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，以及介导这些生物体能力的其他干扰素独立基因侵入不同组织，可能与密切相关的沙眼衣原体发病机制的差异有关隔离。然而，大多数这些基因尚未被识别，因为基因操作方法这些病原体最近才被开发出来。在我们研究的目标之一中，我们将使用正向遗传筛选，新的基因作图工具和小鼠模型，用于识别适应小鼠的沙眼衣原体亲属的基因用于逃避免疫并感染小鼠的不同组织，并剖析这些组织的功能。类似的方法将用于目标 2 来鉴定和表征沙眼衣原体基因的功能，这些基因介导这些生物体附着、侵入并避免来自不同人类的代表性细胞的免疫反应组织。