Salpingeal infection model of Mycoplasma genitalium

生殖支原体输卵管感染模型

• 批准号: 7772292
• 负责人: PATRICIA A TOTTEN
• 金额: $ 7.72万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-20 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7772292
• 关键词: Abdomen; Animal Model; Animals; Antibodies; Antibody Formation; Antigenic Variation; Archives; Autologous; Bacteria; Bacterial Adhesins; Cells; Cervicitis; Cervix Uteri; Chlamydia trachomatis; Chronic; Cloning; Confocal Microscopy; DNA; Data; Detection; Development; Disease; Disease Association; Endometritis; Evaluation; Evolution; Female; Funding; Future; Generations; Genes; Genital system; Growth; Harvest; Hemophilus ducreyi; Housing; Immune; Immune response; Immunobiology; Immunoglobulin Variable Region; Implant; In Vitro; Individual; Infection; Infection prevention; Infertility; Inflammatory; Laboratories; Lead; Leucocytic infiltrate; Location; Macaca; Macaca nemestrina; Mammalian Oviducts; Medicine; Modeling; Molecular; Mycoplasma genitalium; Nature; Neisseria gonorrhoeae; Organism; Pan Genus; Pathogenesis; Pelvic Inflammatory Disease; Premature Birth; Prevalence; Prevention strategy; Primates; Proteins; Reagent; Research; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Role; Salpingitis; Serum; Site; Specimen; Sterility; Study models; Surface; Syndrome; Techniques; Testing; Time; Tissues; Trichomonas vaginalis; Universities; Urethra; Urethritis; Vagina; Variant; Virulence Factors; Washington; Woman; abdominal wall; animal Oviduct; chronic pelvic pain; clinically significant; cytokine; disease characteristic; extracellular; fimbria; human disease; immunogenic; in vivo; microbicide; model development; novel; pathogen; pressure; public health relevance; reproductive; research study; response; subcutaneous; success

DESCRIPTION (provided by applicant): Mycoplasma genitalium is a newly recognized cause of reproductive tract disease syndromes, including urethritis, mucopurulent cervicitis, pelvic inflammatory disease, and endometritis, with possible sequelae that include infertility, chronic pelvic pain, and preterm birth. Studies assessing the pathogenesis, immunobiology, and virulence factors of M. genitalium are currently being performed in several laboratories, yet are limited by the lack of an appropriate animal model. Chimpanzees, which are no longer available for experimental studies, have been previously used to demonstrate the ability of M. genitalium to cause disease and persist in the urethra, vagina, cervix, and oviducts of these animals. Although other primate species have been less extensively studied, M. genitalium has persistently infected, produced characteristic disease, and induced an antibody response in the majority of species tested. The availability of the Washington National Primate Research Center (WaNPRC) housed at the University of Washington, and the salpingeal pocket model developed by Dr. Patton, a co-investigator on this application, provides a unique opportunity to study the immunopathogenesis of M. genitalium infection. Dr. Totten's research demonstrating the disease associations of M. genitalium, the possible role of antigenic variation in the ability of this organism to persist in infected women, and her proven ability to culture this fastidious organism, provide the necessary expertise to study the molecular pathogenesis of this novel organism. We thus propose to assess the pigtailed macaque as an animal model to study the growth, persistence, and humoral antibody response to M. genitalium; determine the local immunobiology of disease; and evaluate the mechanisms used by M. genitalium to persist during infection. The salpingeal pocket model, developed by Dr. Patton and successfully employed for the elucidation of C. trachomatis infection, will be used to assess M. genitalium infection. The studies proposed herein will lead to future studies assessing the innate and adaptive host immune response to infection, the mechanisms used by M. genitalium to avoid the immune response and persist in vivo, the pathogenesis of M. genitalium infection, and the evaluation of microbicides to prevent infection. PUBLIC HEALTH RELEVANCE: Mycoplasma genitalium is a newly recognized sexually transmitted pathogen with a prevalence and significance that rivals that of Chlamydia trachomatis and Neisseria gonorrhoeae. Little is known about the mechanisms used by this bacterium to elicit disease, in part because suitable animal models have not been developed for this pathogen. Importantly, this organism has developed a potential mechanism of antigenic variation that may explain its ability to persist in infected individuals to cause chronic infections. We propose to develop a primate model to study the immunobiology of M. genitalium infection, using techniques that have been highly successful for the study of C. trachomatis. This model, developed at the Washington National Primate Research Center (WaNPRC), will provide a unique opportunity to study the host/bacterial interactions of M. genitalium in an animal and in tissues most closely related to human disease. Further, development of this model will provide future opportunity to assess strategies for prevention and treatment of this emerging pathogen.

描述（由申请人提供）：支原体生殖器是新认识的生殖道疾病综合征的原因，包括尿道炎，粘膜性宫颈炎，骨盆炎性疾病和子宫内膜炎，其中可能包括不育症，慢性骨盆疼痛和自学生育在内的可能的sequelae。目前正在几个实验室进行了评估生殖器的发病机理，免疫生物学和毒力因子的研究，但由于缺乏适当的动物模型而受到限制。黑猩猩不再可用于实验研究，以前已被用来证明生殖器菌引起疾病并持续存在这些动物的尿道，阴道，子宫颈和卵形的能力。尽管其他灵长类动物的研究较少，但生殖器持续感染，产生了特征性疾病，并在大多数测试的物种中诱导了抗体反应。华盛顿国家灵长类动物研究中心（WANPRC）在华盛顿大学的可用性以及该应用程序的共同发明家Patton博士开发的Salpingeal Pocket模型，提供了一个独特的机会来研究M. Genitalium M. Genitalium的免疫机构。感染。 Totten博士的研究证明了生殖器支原体的疾病关联，抗原差异在该生物体中持续在受感染的妇女中的能力以及她培养这种挑剔的生物体的能力的可能作用，为研究分子发病机理提供了必要的专业知识这个新颖的生物。因此，我们建议评估辫子猕猴作为一种动物模型，以研究对生殖器支原体的生长，持久性和体液抗体反应。确定疾病的局部免疫生物学；并评估生殖器分枝杆菌在感染过程中持续存在的机制。由Patton博士开发并成功地用于阐明沙眼梭状芽孢杆菌感染的Salbingeal口袋模型将用于评估生殖器菌感染。本文提出的研究将导致未来的研究评估对感染的先天和适应性宿主的免疫反应，生殖器支原体用于避免免疫反应并持续存在体内的机制，生殖器支原体感染的发病机理以及对杀菌剂的评估。防止感染。公共卫生相关性：支原体生殖器是一种新认可的性传播病原体，具有疾病和意义，可与沙眼衣原体和淋病奈瑟氏菌的病原体相媲美。关于该细菌用于引起疾病的机制知之甚少，部分原因是该病原体尚未开发合适的动物模型。重要的是，该生物已经开发出一种潜在的抗原变异机制，可以解释其在感染个体引起慢性感染的能力。我们建议开发一种灵长类动物模型，以研究对沙眼梭状芽孢杆菌的研究非常成功的技术研究。该模型在华盛顿国家灵长类动物研究中心（WANPRC）开发，将为研究动物和与人类疾病最密切相关的动物中生殖器的宿主/细菌相互作用提供独特的机会。此外，该模型的发展将为未来评估预防和治疗这种新兴病原体的策略提供机会。