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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：
10602412
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 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10602412
关键词：
Antibiotics Attenuated Bacteria Blindness Cells Cervix Uteri Chlamydia Chlamydia Infections Chlamydia muridarum Chlamydia trachomatis Chromosome Mapping Data Disease Disparate Ectopic Pregnancy Epithelial Cells Epithelium 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 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 Rectum Resistance Rodent Sexual Transmission Sexually Transmitted Diseases Syndrome Time Tissues Trachoma Tropism Urethra Urethritis Vaccine Design Vaccines Virulence Factors Woman adaptive immunity clinically relevant cofactor 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.

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。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Sequestration of host metabolism by an intracellular pathogen.

通过细胞内病原体隔离宿主代谢。

DOI：
10.7554/elife.12552
发表时间：
2016-03-16
期刊：
eLife
影响因子：
7.7
作者：
Gehre L;Gorgette O;Perrinet S;Prevost MC;Ducatez M;Giebel AM;Nelson DE;Ball SG;Subtil A
通讯作者：
Subtil A

A Genital Infection-Attenuated Chlamydia muridarum Mutant Infects the Gastrointestinal Tract and Protects against Genital Tract Challenge.