Primate 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、尿道炎、早产，可能的后遗症包括不孕症、慢性盆腔疼痛、早产和宫颈HIV脱落增强。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，以及由本申请的共同研究者Patton博士开发的猪尾猕猴（Macaca nemestrina）宫颈感染模型的可用性，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宫颈感染模型，以评估感染和持久性的M。生殖器，先天性和适应性免疫反应，这种生物体，抗原变异的作用，使M。生殖器逃避抗体反应并持续存在。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和M。生殖器引起疾病并持续存在。该模型的进一步建立和鉴定将为进一步研究M.生殖器感染以及评估有效的预防和治疗策略。

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.