Immunity and Latency to Chlamydial Infections

衣原体感染的免疫和潜伏期

基本信息

批准号：
7589660
负责人：
Gerald Irwin Byrne
金额：
$ 47.97万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
1982
资助国家：
美国
起止时间：
1982-08-01 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7589660
关键词：
4-ethoxymethylene-2-phenyl-2-oxazoline-5-one Address Anabolism Anatomic Sites Animal Model Animals Antibiotic Resistance Antibiotic Therapy Biological Cavia Cell Culture System Cell Culture Techniques Cell Line Cells Chlamydia Chlamydia Infections Chlamydia trachomatis Chronic Chronic Disease Data Development Diagnosis Disease Environment Enzyme Induction Enzymes Epithelial Fibroblasts Gene Expression Genes Genetic Transcription Genital system Genitourinary system Goals Growth Health Human Immune Immune response Immunity Individual Infection Interferon Type II Investigation Knockout Mice Knowledge Link Mediating Methodology Modeling Molecular Mus NOS2A gene Nutrient Pathogenesis Pathologic Pattern Recognition Research Personnel Resistance Risk Site System Techniques Tissue-Specific Gene Expression Treatment Protocols Tryptophan Tryptophan 2,3 Dioxygenase Vaccine Design Vaccines Woman Work antimicrobial arginase base cell type cytokine design functional genomics human AKAP13 protein improved in vivo macrophage monocyte pathogen prevent programs response transmission process vaccine development

项目摘要

Investigation of immunity and latency to chlamydial infection links host immune responses with chlamydial growth modulation. The concept that chlamydial infections progress to chronic disease has been acknowledged for decades in animals, but is supported by only meager data in humans. Cell culture models do provide proof of principle for the chronic infection (latency) hypothesis. The most compelling mechanistic model is referred to as chlamydial persistence and involves induction of non-productive, but reversible, intracellular chlamydial growth elicited by Th1 immune regulated cytokines (e.g. gamma interferon; IFN-g) on chlamydial host cells. This model has been developed in a variety of human cell culture systems and is based on the induction of an enzyme (indoleamine 2,3-dioxygenase, IDO) that decyclizes tryptophan, creating a nutrient deficient intracellular environment to restrict intracellular chlamydial growth. Study of persistence has, however, been hampered in vivo because appropriate animal models are not available. A major reason for this deficit is that although the mouse is a convenient model for C. trachomatis genital tract disease, murine IFN-g-mediated responses are different from responses observed in humans. Murine immune responses to chlamydiae in wild type animals are likely to result in eradicative immunity rather than persistence, although the full repertoire of lethal and static mouse responses are not yet fully elucidated. Therefore, to gain a better appreciation of requirements for development of chronic chlamydial infections in mice the murine antimicrobial activities elicited by IFN-g will be systematically classified in cell culture (e.g. iNOS, arginase, p47, phox, IDO) using several cell types and primary cells from conventional and knock out mice. Cell culture results will be exploited to study mice that are genetically manipulated or chemically treated to elicit responses that provide an environment conducive to development of chronic chlamydial genital tract infection. Results will provide an improved tractable model of chlamydial persistence, furnish a way to understand more completely the pathogenesis of chronic chlamydial infections, and help define requirements for efficacious vaccine design.

对衣原体感染的免疫力和潜伏期的调查与衣原体的免疫反应联系生长调制。衣原体感染发展为慢性病的概念已经是在动物中被承认数十年，但仅受到人类微薄数据的支持。细胞培养模型确实为慢性感染（潜伏）假设提供了原理证明。最引人注目的机械模型被称为衣原体持久性，涉及非生产性，但 Th1免疫调节的细胞因子引起的可逆性，细胞内衣原体生长（例如γ 干扰素； IFN-G）在衣原体宿主细胞上。该模型是在各种人类细胞中开发的培养系统，基于诱导酶（吲哚胺2,3-二氧酶，IDO）的诱导脱囊色氨酸，创造营养不足的细胞内环境以限制细胞内衣原体生长。然而，对持久性的研究在体内受到了阻碍，因为合适的动物模型不可用。造成这种赤字的主要原因是，尽管鼠标是一个方便的模型对于沙眼生殖道疾病，鼠IFN-G介导的反应与反应不同在人类中观察到。野生型动物中对衣原体的鼠免疫反应可能导致尽管全部致命和静态小鼠的全部曲目响应尚未完全阐明。因此，要更好地理解对 IFN-G引起的鼠抗菌活性的慢性衣原体感染的发展使用几种细胞类型和来自常规和敲除小鼠的原代细胞。细胞培养结果将被利用来研究小鼠经过遗传操纵或化学处理以引起提供有利于环境的反应发展慢性衣原体生殖道感染。结果将提供改进的诱因衣原体持久性的模型，提供了一种更完全理解慢性发病机理的方式衣原体感染，并有助于定义有效疫苗设计的要求。