The Contribution of MicroRNA-182 in Genital Chlamydia trachomatis Infection

描述(由申请人提供)沙眼衣原体(Ct)是美国细菌性传播感染的主要原因，在过去10-15年中发病率不断上升。目前还没有针对CT的预防性疫苗的床边解决方案。了解可能影响宿主免疫的内在宿主分子机制将有助于改进抗CT疫苗候选疫苗的下选(S)。为此，人们对调控RNA的非编码小物种，即microRNAs(MiRs)在包括免疫和生殖生物学在内的关键过程中的作用达成了越来越多的共识。此外，现已制定了使用MIR的疫苗接种策略或免疫疗法。我们最近关于miR调节宿主免疫的作用的报告和对Ct-miR的关联研究(S)共同强调了这些免疫调节剂在CT感染中的重要性，并强调了确定它们在抗CT免疫中的作用的必要性。在这项提案中，我们计划具体研究miR-182通过调节宿主蛋白Alpha-2HS-糖蛋白(AHSG)在小鼠生殖道中对衣原体(Cm)定植的作用。此外，我们计划研究miR-182-AHSG在免疫小鼠中的调节，在免疫小鼠中，抗原(Ag)特异性CD4T细胞和干扰素-γ(干扰素-γ)加速CM从生殖道的清除。综上所述，本申请旨在提供关于miR-182在衣原体感染中的作用以及抗CT免疫对miR-182及其宿主靶标的调节的新信息。

DESCRIPTION (provided by applicant) Chlamydia trachomatis (Ct), is the leading cause of bacterial sexually transmitted infections in the U.S., with increasing incidence rates over the las 10-15 years. A bench-to-bedside solution for a preventative vaccine for Ct is not available. Knowledge of inherent host molecular mechanisms that may influence host immunity will be helpful in improving down-selection of "putative" anti-Ct vaccine candidate(s). To this end, there is growing consensus on the role of small non-coding species of regulatory RNA, i.e. microRNAs (miRs) in critical processes including immunity and reproductive biology. Additionally, vaccination strategies or immunotherapy using miRs have now been established. Our recent report on the role of miR modulating host immunity and association studies on Ct-miR(s) collectively highlight the importance of these immune modulators in Ct infections and underscores the need to define their contribution in anti-Ct immunity. In this proposal, we plan to investigate specifically, the role of miR-182 in colonization of Chlamydia muridarum (Cm) via regulation of host protein, Alpha-2HS-Glycoprotein (AHSG) in the murine genital tract. Additionally, we plan to investigate the regulation of miR-182-AHSG in vaccinated mice where antigen (Ag)-specific CD4+T cells and interferon-γ (IFN-γ) in accelerate Cm clearance from the genital tract. Taken together, this application aims at providing novel information on the role of miR-182 in chlamydial infections and modulation of miR-182 and its host targets by anti-Ct immunity.