Pathogenesis of Obstruction/Emphysema and the Microbiome (POEM) in HIV

HIV 阻塞/肺气肿和微生物群 (POEM) 的发病机制

• 批准号: 8308436
• 负责人: Elodie Ghedin
• 金额: $ 78.66万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-23 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8308436
• 关键词: Alveolar; Anatomy; Apoptotic; Bacteria; Bacterial Translocation; Blood; Bronchoscopy; Cells; Characteristics; Chronic Obstructive Airway Disease; Clinical; Complementarity Determining Regions; Complex; DNA Sequence; Data; Detection; Diffuse; Disease; Disease Progression; Enrollment; Epidemiology; Event; Family; Flow Cytometry; Foundations; Future; Genome; Goals; HIV; HIV Infections; HIV-1; Immunologics; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Instruction; Irrigation; Lead; Location; Lung; Lung diseases; Measures; Metabolic Pathway; Metagenomics; Microbe; Molecular Genetics; Nature; Obstruction; Oral; Organism; Oropharyngeal; Pathogenesis; Patients; Pattern; Peptide Hydrolases; Peripheral; Persons; Phenotype; Plasma; Play; Pneumocystis; Population; Principal Investigator; Protozoa; Pulmonary Emphysema; Recombinant DNA; Relative (related person); Research Infrastructure; Resources; Respiratory System; Respiratory physiology; Respiratory tract structure; Ribosomal RNA; Role; Sampling; Spirometry; Sputum; Structure; T-Cell Activation; Techniques; Technology; Testing; Virus; Whole-Genome Shotgun Sequencing; X-Ray Computed Tomography; cohort; cytokine; follow-up; immune activation; interest; microbial; microbial community; microbiome; respiratory

DESCRIPTION (provided by applicant): Microbial flora in persons with HIV likely play an important role in various diseases, but the nature of the microbiome in the lungs of persons with HIV has not been studied. High-throughput, DNA sequencing technologies now allow examination of complex microbial communities including organisms that cannot be cultured. These techniques have potential to yield important information about events in the lung during HIV and its associated pulmonary disorders. Chronic obstructive pulmonary disease (COPD) is of particular interest in the current era of HIV infection. Pathogenesis of HIV-associated COPD is poorly understood, but one or more infections may upregulate expression of HIV in the lungs, amplify the pulmonary inflammatory response, and lead to release of proteases or pro-apoptotic factors. Data from our group suggest that low level infection with Pneumocystis is increased in HIV-F subjects and associated with anatomic emphysema. Other infections alone or in combination are likely to be important in disease pathogenesis. Application of metagenomic techniques will allow us to determine patterns and changes in the population of microbes that play a key role in the pathogenesis and progression of emphysema in this population. The overall goals of this proposal are to determine the respiratory microbial flora (or microbiota) in HIV-I- and HIV- subjects and to establish its role in pathogenesis and progression of HIV-associated COPD using our ongoing cohorts. Specific aims of the proposal are: 1. To compare the microbial community structure in the respiratory tract in subjects with and without HIV infection. 2. To test the hypothesis that the respiratory microbiome in HIV-I- subjects with COPD differs from that in HIV-f subjects without COPD and is related to COPD progression. 3. To test the hypothesis that bacterial products in the blood are detectable in HIV-f subjects with COPD and are associated with immune activation. We will perform oral wash, sputum induction, bronchoscopy, and blood draws in HIV- and HIV-I- subjects and carry out high-throughput virus metagenomics and bacterial, fungal and protozoal 16S rDNA analyses for characterization of microbiome population diversity. Results will be used to determine which microbes are present, their relative proportions, their location, and their relationship to HIV and COPD. RELEVANCE (See instructions): This proposal will help us determine which infections are present In the lungs of people with HIV and how the infections might explain why HIV-infected individuals develop emphysema faster than non-HIV-infected people. This information will help us understand and treat emphysema in these patients and in the many non-HIV-infected people who suffer from emphysema.

描述（由申请方提供）：HIV感染者体内的微生物植物群可能在各种疾病中发挥重要作用，但尚未研究HIV感染者肺部微生物组的性质。高通量DNA测序技术现在允许检查复杂的微生物群落，包括不能培养的生物体。这些技术有可能产生有关HIV及其相关肺部疾病期间肺部事件的重要信息。慢性阻塞性肺疾病（COPD）是特别感兴趣的艾滋病毒感染的当前时代。HIV相关COPD的发病机制尚不清楚，但一种或多种感染可上调肺中HIV的表达，放大肺部炎症反应，并导致蛋白酶或促凋亡因子的释放。我们小组的数据表明，HIV-F受试者中肺孢子虫的低水平感染增加，并与解剖性肺气肿相关。其他感染单独或联合可能是重要的疾病发病机制。宏基因组技术的应用将使我们能够确定在该人群中肺气肿的发病机制和进展中起关键作用的微生物群体的模式和变化。本提案的总体目标是确定HIV-I和HIV-受试者的呼吸道微生物植物群（或微生物群），并使用我们正在进行的队列确定其在HIV相关COPD发病机制和进展中的作用。该提案的具体目标是：1。比较HIV感染者和非HIV感染者呼吸道微生物群落结构。2.检验以下假设：患有COPD的HIV-I受试者的呼吸道微生物组与不患有COPD的HIV-f受试者的呼吸道微生物组不同，并且与COPD进展相关。3.检验血液中的细菌产物在患有COPD的HIV-f受试者中可检测到并且与免疫激活相关的假设。我们将在HIV和HIV-I受试者中进行口腔冲洗，诱导痰液，支气管镜检查和抽血，并进行高通量病毒宏基因组学和细菌，真菌和原生动物16 S rDNA分析，以表征微生物组群体多样性。结果将用于确定存在哪些微生物，它们的相对比例，它们的位置以及它们与HIV和COPD的关系。相关性（参见说明）：这一建议将帮助我们确定哪些感染存在于艾滋病毒感染者的肺部，以及这些感染如何解释为什么艾滋病毒感染者比非艾滋病毒感染者更快地患上肺气肿。这些信息将帮助我们了解和治疗这些患者以及许多患有肺气肿的非HIV感染者的肺气肿。