PRIMATE MODEL FOR MYCOPLASMA GENITALIUM

生殖支原体灵长类动物模型

• 批准号: 8357617
• 负责人: PATRICIA A TOTTEN
• 金额: $ 15.66万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357617
• 关键词: Animal Model; Animals; Antibodies; Antibody Formation; Bacterial Adhesins; Biopsy; Cells; Cervical; Cervix Uteri; Detection; Funding; Grant; Histology; Immune; Infection; Infiltration; Macaca nemestrina; Mammalian Oviducts; Modeling; Mycoplasma genitalium; National Center for Research Resources; Primates; Principal Investigator; Process; Production; Protocols documentation; Research; Research Infrastructure; Resources; Schedule; Serum; Source; Specimen; Time; Tissues; United States National Institutes of Health; Vagina; Variant; cost; fimbria; pathogen; reproductive; research study; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In our grant, IR21AI074898, "A Primate Model of Mycoplasma genitalium" we are assessing the ability of pigtail macaques to serve as an animal model to study the immunopathogenesis of M. genitalium (MG), a newly recognized reproductive tract pathogen. In this model primates are inoculated cervically with MG then vaginal and cervical specimens are collected at intervals spanning 8 weeks for detection of MG by qPCR and culture. Biopsies are collected at Week 4 (Fallopian tube and fimbriae) and Week 8 (Fallopian tube, fimbriae and cervix) at which time the animals are treated to cure the MG infection. The biopsies are processed for culture, qPCR and histology to detect immune cell infiltration. Serum is collected prior to infection at and intervals to assess the production of anti-MG antibodies over the course of the infection. In the past year we have inoculated 4 of the 6 primates funded by this proposal with MG: 2 primates were successfully colonized throughout the 8 weeks of the study, one was colonized for 4-6 weeks and the fourth animal was not infected. Preliminary analysis of serum suggests that antibodies to MG are produced after infection that specifically recognized the immunodominant adhesin molecules, MgpB and MgpC. Culture and qPCR of the upper reproductive tract tissues suggests that MG has not ascended from the lower tract in these animals suggesting that longer experiments or repeated inoculations may be necessary to induce upper tract infection. Finally, experiments are underway to assess sequence variation in MgpB and MgpC during infection in response to antibody production. The final two primates funded by this grant are scheduled to undergo our protocol, scheduled for Feb-Aug 2011.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 在我们的基金IR21AI074898“生殖支原体的灵长类动物模型”中，我们正在评估小尾猴作为动物模型研究生殖支原体(MG)的免疫发病机制的能力。在该模型中，灵长类动物经宫颈接种MG，然后每隔8周采集阴道和宫颈标本，用定量聚合酶链式反应和培养法检测MG。在第4周(输卵管和海马伞)和第8周(输卵管、海马伞和宫颈)收集活检组织，然后对动物进行治疗以治愈MG感染。活检组织进行培养、定量聚合酶链式反应和组织学检查，以检测免疫细胞的渗透情况。在感染前每隔一段时间收集血清，以评估感染过程中抗MG抗体的产生情况。在过去的一年里，我们已经将该计划资助的6只灵长类动物中的4只接种了MG：在整个研究的8周内，2只灵长类动物被成功定植，1只被定植4-6周，第四只动物没有感染。对血清的初步分析表明，MG抗体是在感染后产生的，特异性地识别免疫优势的粘附素分子mgpB和mgpC。上段生殖道组织的培养和定量聚合酶链式反应表明，在这些动物中，MG并没有从下道上升，这表明可能需要更长的实验或重复接种才能诱导上路感染。最后，正在进行实验，以评估在感染期间对抗体产生的反应而产生的mgpB和mgpC的序列变化。由这笔资金资助的最后两个灵长类动物计划在2011年2月至8月接受我们的方案。