The Oral Mucosa in HIV Disease: Innate Immunity

HIV 疾病中的口腔粘膜：先天免疫

• 批准号: 7265176
• 负责人: Nina Agabian
• 金额: $ 84.53万
• 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 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7265176
• 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（由申请人提供）：虽然口腔粘膜有效地排除了 HIV 感染，但它是一组选定的机会性感染 (OIs) 的宿主，这些机会性感染 (OIs) 出于不明原因，在 HIV 感染中表现得很明显，并且是进展为 AIDS 和免疫重建治疗失败的哨兵。作为我们的统一焦点，我们将探讨有助于口腔先天免疫的因素。在这个题为“艾滋病毒口腔粘膜：先天免疫”的项目申请中，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。作为我们的统一焦点，我们将探讨有助于口腔先天免疫的因素。通过设计，这四个项目中提出的实验范围广泛，从旨在发现和表征对病毒和微生物病原体的先天免疫功能的口腔分泌物成分的广泛方法（项目1：HIV疾病对唾液蛋白质组的影响），到特定抗病毒/微生物肽作用机制的描述和分子表征（项目2：口腔S100A8和S100A9） 在 HIV 感染和项目 3：HIV 诱导的先天口腔免疫防御改变）中，描述了 HIV 诱导的 I 型干扰素系统改变的特征（项目 3）。这些项目获得的有关宿主对 HIV/HAART 反应要素的信息，通过直接表征这些宿主分子对病原体本身、HIV、HPV 和白色念珠菌 (C. albicans) 的影响进行了补充（项目 1、2、3 和项目 4：念珠菌-宿主相互作用的分子表征）。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 OIs 的共同感染如何影响 HIV 疾病中的口腔粘膜功能（项目 4）。根据 RFA 的要求，以及我们历史上的做法，我们将充分利用质谱、基因组学和 DNA 微阵列分析、实时 RT-PCR 和激光解剖显微镜 (LDM) 等尖端技术来研究 HIV 疾病中的口腔粘膜。采取协调一致的方法，我们的计划项目的总体目标将是识别和表征口腔中表达的先天免疫因子的范围，并通过这样做了解这些因素如何单独和共同促进口腔粘膜对艾滋病毒感染和 OIs 的潜在抵抗力，而艾滋病毒感染和 OIs 在口腔中是免疫失败的主要和直接表现。