The oral mucosal proteome: perturbation in HIV infection and Candida co infection

描述（由申请人提供）：此多学科申请支持将以患者为导向的研究与基于科学的疾病病因调查相结合的策略。总的目的是了解保护口腔上皮免受HIV感染的机制。长期目标是了解免疫功能受损宿主体内的共生基础，从而提供更有效的治疗方法。我们假设HIV直接影响口腔上皮蛋白质组，导致改变，促进共同病原体念珠菌的定植和感染。具体目的是：1)充分表征保护口腔黏膜免受HIV和念珠菌感染的口腔上皮成分。利用口腔和阴道上皮模型，以及人类和猕猴样本，流式细胞术将研究HIV和念珠菌的典型受体。在存在或不存在HIV和念珠菌的情况下，上皮蛋白组将被充分表征，以便确定这些粘膜中对HIV和念珠菌感染的保护或易感性因素。唾液将被应用到模型中，以研究存在于口腔液中可能抑制HIV或念珠菌感染的先天分泌因子的贡献，转录物分析、定量RT-PCR和Luminex蛋白分析将被用于支持蛋白质组学数据。2)研究HIV和念珠菌感染过程中人上皮诱导的tlr相关先天蛋白组学反应。HIV-和C. a/b/can诱导的上皮细胞因子、趋化因子、TLR1-10和信号通路表达谱将首先在口腔和阴道上皮模型中使用蛋白质组学进行表征。pmn依赖的tlr介导的抗口腔白色念珠菌感染的保护机制将通过转录谱分析、实时RT-PCR、共聚焦和免疫电子显微镜以及siRNAi来充分表征。相关性：艾滋病毒/艾滋病最常通过粘膜传播。在某些情况下，口腔组织暴露于艾滋病毒，但很少被感染。了解口腔免受感染的机制可能会导致开发出保护其他粘膜组织（如阴道）免受感染和病毒传播的治疗方法。这也可能导致治疗与HIV相关的合并感染的疗法，如鹅口疮。

DESCRIPTION (provided by applicant): This multidisciplinary application supports a strategy of combining patient-oriented research with the science based investigation of disease causation. The overall aim is to understand the mechanisms that apparently protect the oral epithelium from HIV infection. The long-term objective is to understand the basis of copathogenicity in the immunocompromised host leading to the delivery of more effective therapies. We hypothesize that HIV directly affects the oral epithelial proteome, leading to alterations that promote colonization and infection of the co-pathogen Candida. The specific aims are: 1) To fully characterize the constituents of the oral epithelium that protects the oral mucosa from HIV and Candida infection. Using oral and vaginal epithelial models, and human and macaque samples, the canonical receptors for both HIV and Candida will be investigated by flow cytometry. The epithelial proteome in the presence or absence of HIV and Candida will be then be fully characterized in order to identify protective or susceptibility factors to HIV and Candida infection in these mucosae. Saliva will be applied to the models to investigate the contribution of innate secretory factors present in oral fluids that may inhibit HIV or Candida infection Transcript profiling, quantitative RT-PCR, and Luminex protein assays will be performed to support the proteomic data. 2) To characterize the innate TLR-associated proteomic response elicited by human epithelium during HIV and Candida infection. The HIV- and C. a/b/cans-induced epithelial cytokine, chemokine, TLR1-10 and signaling pathway expression profiles will first be characterized in oral and vaginal epithelial models using proteomics. The PMN-dependent TLR-mediated protection mechanism against oral C. albicans infection will then be fully characterized using transcript profiling, real-time RT-PCR, confocal and immunoelectron microscopy, and siRNAi. Relevance: HIV/AIDS is most commonly transmitted through mucosal membranes. In some circumstances, the oral tissues are exposed to HIV but rarely become infected. Understanding the mechanism by which the oral cavity is apparently protected from infection could lead to the development of therapies to protect other mucosal tissues such as the vagina from infection and transmission of the virus. This could also lead to therapies for the treatment of the co-infections associated with HIV such as oral Thrush.