Determination of immunogenic microbiota in the lung: leveraging the Lung HIV Microbiome Project

肺部免疫原性微生物群的测定：利用肺部 HIV 微生物组项目

• 批准号: 9587593
• 负责人: Barbara Methe
• 金额: $ 11.74万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9587593
• 关键词: Activities of Daily Living; Address; Alveolar; Archaea; Aspirate substance; Bacteria; Bacteriophages; Bioinformatics; Biological; Biological Assay; Biological Process; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Cell Separation; Chronic Obstructive Airway Disease; Chronic lung disease; Clinical Data; Collection; Communities; Complex; DNA; Data; Development; Disease; Ecology; Environment; Exposure to; Foundations; Gene Expression; Genes; Genetic Transcription; HIV; Health; Human; Immune; Immune response; Immune system; Immunity; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Individual; Irrigation; Lung; Lung diseases; Magnetism; Measures; Metabolic; Metabolism; Methodological Studies; Methodology; Methods; Microbe; Morbidity - disease rate; Multicenter Studies; Nature; Oral cavity; Organism; Outcome; Pathogenesis; Play; Pulmonary Emphysema; Pulmonary function tests; RNA; Respiratory Signs and Symptoms; Respiratory physiology; Role; Sampling; Series; Signaling Molecule; Smoker; Specimen; Sterility; Structure; Systemic disease; Taxonomy; Techniques; Technology; Tissue-Specific Gene Expression; airway obstruction; antiretroviral therapy; base; chemokine; comparative; cytokine; design; disease phenotype; fungus; host microbiome; immunogenic; immunological status; lung basal segment; lung microbiome; lung microbiota; metatranscriptomics; method development; microbial community; microbiome; microbiome components; microbiome research; microbiota; microorganism; mortality; never smoker; non-smoker; novel; rRNA Genes; transcriptome sequencing

PROJECT SUMMARY Chronic obstructive pulmonary disease (COPD), which encompasses airway obstruction and/or emphysema, is a growing cause of morbidity and mortality in HIV+ individuals in the current era. Pathogenesis of HIV- associated COPD is poorly understood, but shifts in the lung microbiome may play a role. The lung interacts with the host immune system and receives constant exposure to the environment and to microorganisms aspirated from the oral cavity. We do not yet know how these exposures might impact the lung and how microorganisms in the lung might differ in HIV and in COPD. The current study will leverage data and biospecimens from the Lung HIV Microbiome Project (LHMP), the first multicenter study of the lung microbiota. This project will add to the LHMP framework by undertaking a microbiome-based (microbial communities, their gene content, and environmental interactions) examination of the lung while simultaneously developing or enhancing the use of high throughput ‘omics-based technologies. First, we will examine how host recognition of microorganisms differs between HIV-infected and uninfected individuals and individuals with and without COPD. Using LHMP bronchoalveolar lavage (BAL) specimens, we will identify key bacteria and fungi that drive host response using a novel magnetic activated cell sorting (MACS) assay to target and separate immunoglobulin (Ig)-bound bacteria and fungi. We will then use sequencing techniques to compare taxonomy of Ig-bound bacteria between individuals with and without HIV and with and without COPD. Selected chemokines and cytokines (small signaling molecules) produced by the human host will also be measured to provide a snapshot of host immune system status. We will then characterize the biological functions of the microbiome more broadly using whole community RNA to measure metabolic activity of not only bacteria, but also potential contributions from fungi, archaea and bacteriophage. A series of comparative bioinformatic and statistical approaches will be used to characterize and compare community structure and function between individuals with and without HIV and COPD. Development of these methods will reveal not only shifts in taxonomic structure in relation to host immune recognition, but through sequencing RNA, also identify biological function. Understanding collective microbial community function will allow us to better address the question of how does the metabolism of the community that resides in the lung of individuals with HIV and COPD differ from individuals without these conditions, and in what ways may their metabolic activity contribute to changes in lung function. Collectively, this study will examine lung microbial communities in individuals with differing HIV and COPD status, forming the foundation for larger-scale mechanistic studies while developing methodology directly applicable to other microbiome-based lung studies of health and disease.

项目摘要 慢性阻塞性肺部疾病（COPD），涵盖气道阻塞和 /或肺气肿 在当前时代的艾滋病毒+个体的病态和死亡率的日益增长的原因。 相关的COPD知之甚少，但是肺微生物组的变化可能起作用 使用主机图像系统，并接收到环境和微生物 从口腔中抽出。 肺中的微生物在HIV和COPD中可能有所不同。 肺Hiviome项目（LHMP）的生物测量，这是肺微生物群的第一项多中心研究。 该项目将通过基于微生物组的（微生物群落及其）来解决LHMP框架 基因含量和环境相互作用）检查肺的检查，同时开发或 通过技术来增强高位的使用。 在有和没有的艾滋病毒感染者和未感染的个体和没有和没有的人之间，微生物的不同 COPD。使用LHMP支气管肺泡灌洗（BAL）标本 使用新型的磁性细胞分选（MAC）测定到靶标的和Seprate的宿主响应 免疫球蛋白（IG） - 结合细菌和真菌。 没有没有COPD的个体之间的IG结合细菌。 人宿主Wilso产生的趋化因子和细胞因子（小信号分子） 提供宿主免疫系统状态的快照。 微生物组更广泛地使用整个社区RNA来测量不仅细菌的代谢活性，而且还测量 真菌，古细菌和噬菌体的潜在贡献。 统计方法将用于表征和比较社区，结构和功能。 与艾滋病毒和COPD的人相关的人。 与宿主免疫识别有关的分类结构，但对RNA进行测序，也识别 生物学功能。 问题的问题是如何驻留在艾滋病毒艾滋病毒和艾滋病毒和 COPD与这些条件下的个人不同，其代谢活动可能有什么作用 肺部功能的变化。 不同的艾滋病毒和COPD状况，为大规模机械研究构成基础 方法直接适用于其他基于微生物组的健康和疾病肺研究。