Salpingeal infection model of Mycoplasma genitalium

描述（由申请方提供）：生殖支原体是一种新认识到的生殖道疾病综合征的病因，包括尿道炎、粘液脓性宫颈炎、盆腔炎和尿道炎，可能的后遗症包括不孕症、慢性盆腔疼痛和早产。研究评估的发病机制，免疫生物学，和毒力因子的M。目前，生殖器的移植在几个实验室中进行，但由于缺乏适当的动物模型而受到限制。黑猩猩，这是不再可用于实验研究，以前曾被用来证明M。生殖器引起疾病，并持续存在于这些动物的尿道、阴道、子宫颈和输卵管中。虽然其他灵长类动物的研究较少，M。生殖器持续感染，产生特征性疾病，并在大多数测试物种中诱导抗体应答。位于华盛顿大学的华盛顿国家灵长类动物研究中心（WaNPRC）的可用性，以及该应用的共同研究者Patton博士开发的输卵管袋模型，为研究M.生殖器感染Totten博士的研究证明了M.生殖器，抗原变异在这种生物体在感染妇女中持续存在的能力中的可能作用，以及她证明的培养这种挑剔的生物体的能力，为研究这种新生物体的分子发病机制提供了必要的专业知识。因此，我们建议评估猪尾猕猴作为动物模型，以研究的增长，持久性和体液抗体反应的M。生殖器;确定疾病的局部免疫生物学;并评估M.生殖器在感染期间持续存在。Patton博士开发的输卵管袋模型成功地用于阐明C。沙眼衣原体感染，将用于评估M。生殖器感染本文提出的研究将导致未来的研究评估先天性和适应性宿主对感染的免疫反应，M。生殖器以避免免疫反应并在体内持续存在，M.生殖器感染，以及评价杀微生物剂预防感染。公共卫生相关性：生殖支原体是一种新发现的性传播病原体，其流行率和重要性可与沙眼衣原体和淋病奈瑟菌相媲美。人们对这种细菌引发疾病的机制知之甚少，部分原因是还没有为这种病原体开发合适的动物模型。重要的是，这种微生物已经发展出一种潜在的抗原变异机制，这可能解释其在感染个体中持续存在以引起慢性感染的能力。我们建议建立一个灵长类动物模型来研究M.生殖器感染，使用的技术已经非常成功的研究C。沙眼该模型由华盛顿国家灵长类动物研究中心（WaNPRC）开发，将为研究M.在动物和与人类疾病最密切相关的组织中的生殖器。此外，该模型的开发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。

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.