The Oral Mucosa in HIV Disease: Innate Immunity

HIV 疾病中的口腔粘膜：先天免疫

• 批准号: 7107889
• 负责人: Nina Agabian
• 金额: $ 87万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-08 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7107889
• 关键词: Oral; Mucosa; HIV; Disease; Innate

DESCRIPTION (provided by applicant): While the oral mucosa effectively excludes HIV infection, it is host to a select group of opportunistic infections (OIs), which, for reasons not understood, are manifest in HIV infection and are sentinel of the progression to AIDS and failure of immune reconstitution therapy. As our unifying focus, we will explore the factors that contribute to innate immunity in the oral cavity. In this Program Project Application entitled: The Oral Mucosa in HIV Disease: innate Immunity, we propose four highly-integrated, multidisciplinary projects which are supported by two cores: Core A: the Administrative and Technical Support Core and Core B: the Clinical Core. As our unifying focus, we will explore the factors that contribute to innate immunity in the oral cavity. By design, the experiments proposed in the four projects range from broad-based approaches which aim to discover and characterize components of oral secretions which function in innate immunity to viral and microbial pathogens (Project 1: The Impact of HIV Disease on the Salivary Proteome), to the description and molecular characterization of the mechanism of action of specific anti-viral/microbial peptides (Project 2: Oral S100A8 and S100A9 in HIV Infection and Project 3: HIV-induced Alterations of Innate Oral Immune Defenses), to the characterization of HIV-induced alterations in the type I interferon system (Project 3). Information gained by these projects on the elements of the host response to HIV/HAART are complemented by direct characterization of the effect of these host molecules on the pathogens themselves, HIV, HPV and Candida albicans (C. albicans) (Project 1, 2, 3, and Project 4: Molecular Characterization of Candida-Host Interactions). Finally the direct effect of C. albicans on oral epithelial cells will be evaluated with the objective of learning how co-infection with OIs affect oral mucosal function in HIV disease (Project 4). As mandated by the RFA, and as has been our approach historically, we will bring the full force of cutting edge technologies such as mass spectrometry, genomics and DNA microarray analysis, Real Time RT-PCR and laser dissection microscopy (LDM) to bear on the study of the oral mucosa in HIV disease. Taking a concerted approach, the overarching goal of our program project will be to identify and characterize the range of innate immune factors expressed in the oral cavity and by so doing learn how these singly and together contribute to the underlying resistance of the oral mucosa to HIV infection and OIs which, in the oral cavity, are primary and immediate manifestations of immune failure.

描述(申请人提供)：虽然口腔粘膜有效地排除了艾滋病毒感染，但它是一组精选的机会性感染(OIS)的宿主，这些感染的原因尚不清楚，在HIV感染中表现得很明显，是发展为艾滋病和免疫重建治疗失败的前哨。作为我们统一的焦点，我们将探索口腔内天然免疫的影响因素。在这个题为：HIV疾病中的口腔粘膜：先天免疫的计划项目申请中，我们提出了四个高度整合的多学科项目，这些项目由两个核心支持：核心A：行政和技术支持核心和核心B：临床核心。作为我们统一的焦点，我们将探索口腔内天然免疫的影响因素。通过设计，四个项目中建议的实验范围从旨在发现和表征在对病毒和微生物病原体的先天性免疫中起作用的口腔分泌物的成分的广泛方法(项目1：艾滋病毒疾病对唾液蛋白质组的影响)到特定抗病毒/微生物多肽作用机制的描述和分子表征(项目2：艾滋病毒感染中的口服S100A8和S100A9以及项目3：艾滋病毒诱导的口腔免疫防御系统的改变)，到表征艾滋病毒诱导的I型干扰素系统的变化(项目3)。通过这些项目获得的关于宿主对艾滋病毒/HAART反应要素的信息得到了这些宿主分子对病原体本身、艾滋病毒、人乳头瘤病毒和白色念珠菌(白色念珠菌)影响的直接表征的补充(项目1、2、3和项目4：念珠菌-宿主相互作用的分子特征)。最后，将评估白色念珠菌对口腔上皮细胞的直接影响，目的是了解与OIS合并感染如何影响HIV疾病患者的口腔粘膜功能(项目4)。按照RFA的要求，以及我们历史上的做法，我们将充分利用尖端技术，如质谱学、基因组学和DNA微阵列分析、实时RT-PCR和激光解剖显微镜(LDM)，对HIV疾病的口腔粘膜进行研究。采取协调一致的方法，我们计划项目的总体目标将是识别和表征在口腔中表达的先天免疫因素的范围，并通过这样做来了解这些因素如何单独和共同促进口腔粘膜对HIV感染和OIS的潜在抵抗力，而OIS在口腔中是免疫失败的主要和直接表现。