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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：
9463293
负责人：
David Emmet Nelson
金额：
$ 57.91万
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 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9463293
关键词：
Alleles Attenuated Azithromycin Bacteria Blindness Cells Cervix Uteri Chlamydia Chlamydia Infections Chlamydia trachomatis Chromosome Mapping Clinical Complement Diagnosis Disease Dissection Ectopic Pregnancy Epidemiology Epithelial Epithelial Cells Fibroblasts Funding Gastrointestinal tract structure Genes Genetic Genetic Recombination Genetic Screening Genome Genomics Goals Human Immune Immune Evasion Immune Targeting Immune response Immune system Immunity In Vitro Infection Interferon Type II Interferons Invaded Knockout Mice Link Lymphogranuloma Venereum Mammalian Oviducts Mediating Medical Methods Modeling Molecular Monitor Mus One-Step dentin bonding system Organism Pathogenesis Pelvic Inflammatory Disease Peripheral Phenotype Physiological Resistance Rodent Sexually Transmitted Diseases Testing Tissues Trachoma Transgenes Tropism Urethra Urethritis Vaccine Design Vaccines Virulent Woman adaptive immune response adaptive immunity cost cytokine experimental study gastrointestinal gastrointestinal infection gene function genetic analysis genetic approach genetic manipulation genome editing genome-wide human disease human female human tissue improved innovation insight male men mouse model mutant novel novel strategies pathogen prevent rectal reproductive tract tissue tropism tool

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 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.

摘要