Primate Model of Mycoplasma genitalium

描述(由申请人提供)：生殖支原体是一种新发现的生殖道疾病综合征的病因，包括尿道炎、粘液脓性宫颈炎症、盆腔炎、子宫内膜炎、早产，可能的后遗症包括不孕不育、慢性盆腔疼痛、早产和艾滋病毒宫颈脱落增加。评价生殖支原体的致病机制、免疫生物学和毒力因子的研究目前正在几个实验室进行，但由于缺乏合适的动物模型而受到限制。黑猩猩不再用于实验研究，以前曾被用来证明生殖支原体致病的能力，并持续存在于这些动物的尿路、阴道、宫颈和输卵管中。虽然对其他灵长类物种的研究较少，但生殖支原体在大多数被测试物种中持续感染，产生特有的疾病，并诱导抗体反应。设在华盛顿大学的华盛顿国家灵长类动物研究中心(WaNPRC)的出现，以及由Patton博士开发的辫尾猕猴(Macaca Nomestrina)宫颈感染模型的出现，为研究生殖支原体感染的免疫发病机制提供了独特的机会。Totten博士的研究证明了生殖支原体的疾病关联，抗原变异在这种微生物在受感染女性身上持续存在的能力中可能扮演的角色，以及她被证明有能力培养这种挑剔的有机体，为研究这种新生物的分子发病机制提供了必要的专业知识。因此，我们建议评估辫尾猕猴宫颈感染模型，以评估生殖支原体的感染和持久性，对这种生物的先天和获得性免疫反应，以及抗原变异在允许生殖支原体逃避抗体反应和持久性方面的作用。公共卫生相关性：这些研究将进一步加深我们对感染的免疫生物学以及生殖支原体致病和持续存在的可能机制的理解。这一模型的进一步建立和表征将导致对生殖支原体致病机制的未来研究，以及对有效的预防和治疗策略的评估。

DESCRIPTION (provided by applicant): Mycoplasma genitalium is a newly recognized cause of reproductive tract disease syndromes, including urethritis, mucopurulent cervicitis, pelvic inflammatory disease, endometritis, preterm birth, with possible sequelae that include infertility, chronic pelvic pain, preterm birth, and enhanced cervical shedding of HIV. 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, the availability of the cervical infection model of pigtailed macaques (Macaca nemestrina) 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 cervical infection model to evaluate infection and persistence of M. genitalium, the innate and adaptive immune response to this organism, and the role of antigenic variation in allowing M. genitalium to evade the antibody response and persist. PUBLIC HEALTH RELEVANCE: These studies will further our understanding of the immunobiology of infection and the possible mechanisms used by M. genitalium to cause disease and persist. Further establishment and characterization of this model will lead to future studies assessing the pathogenesis of M. genitalium as well as the evaluation of effective strategies for prevention and treatment.