The Effects of M. tuberculosisInfection on Lung Microbiome in Macaques

结核分枝杆菌感染对猕猴肺部微生物组的影响

• 批准号: 9018134
• 负责人: JoAnne L. Flynn
• 金额: $ 9.14万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9018134
• 关键词: Address; Affect; Animal Model; Area; Asthma; Bacteria; Bioinformatics; Cell physiology; Cells; Cessation of life; Chronic Obstructive Airway Disease; Collaborations; Collection; Complex; Data; Development; Disease; Dose; Environment; Event; Frequencies; Funding; Future; Goals; Grant; Granuloma; HIV; HIV Infections; Heart Diseases; Human; Human Microbiome; Imaging technology; Immune response; Immunocompromised Host; Infection; Infection Control; Inflammation; Inflammatory; Investigation; Lung; Macaca; Measures; Modeling; Modification; Monkeys; Morbidity - disease rate; Mycobacterium tuberculosis; Nature; Obesity; Organ; Outcome; Outcome Measure; Pathology; Persons; Pharmaceutical Preparations; Play; Positron-Emission Tomography; Predisposition; Primary Infection; Regimen; Research; Risk; Role; Sampling; Sequence Analysis; Shapes; Surveys; Symptoms; Syndrome; TNF gene; Technology; Testing; Time; Tuberculosis; Universities; X-Ray Computed Tomography; fluorodeoxyglucose; fluorodeoxyglucose positron emission tomography; global health; gut microbiome; latent infection; lifetime risk; microbiome; mortality; nonhuman primate; primary outcome; public health relevance; response; secondary outcome; treatment strategy

 DESCRIPTION (provided by applicant): Tuberculosis remains a major cause of morbidity and mortality worldwide. Despite years of research, our understanding of the complex interactions between the human host and Mycobacterium tuberculosis remains incomplete. In particular, the events that occur early in infection between the bacteria and the host are very poorly understood, primarily due to their clinically silent nature. However, our data in a non-human primate model of tuberculosis point to early events as crucial and predictive of eventual outcome of infection. Recent studies have implicated the human microbiome as playing a pivotal role in influencing and shaping the immune response and host outcome to infections, as well as in other diseases including obesity, heart disease, and COPD. Although most studies have focused on the gut microbiome, more recently the lung microbiome has been a rich area for research. To date, there is little data on whether there is significant interaction between M. tuberculosis infection and the lung microbiome. In this proposal, we will use a non-human primate model of M. tuberculosis infection, which faithfully recapitulates all aspects of human tuberculosis, to survey the changes that M. tuberculosis infection elicits upon the lung microbiome. This project will provide a thorough assessment of whether this infection alters the lung microbiome in macaques, including the magnitude and duration of change. We will initially collect serial airway samples prior to and throughout infection and subsequently sequence and analyze the microbiome of these samples to address these questions. Using PET/CT imaging technologies to assess serial progression of the infection, we will correlate magnitude and duration of change in the microbiome to inflammation within the lungs. This project will provide a unique opportunity to begin to tackle the dynamics between the lung microbiome and M. tuberculosis and will lay the framework for future studies to assess the importance of the lung microbiome to susceptibility, immune responses and infection outcome in M. tuberculosis infection. This project represents a new direction for TB research in a model that replicates human TB, and is a collaboration among labs with expertise in the macaque model of TB and those with expertise in taxonomic characterization of the lung microbiome.

 描述（由申请人提供）：结核病仍然是全世界发病和死亡的主要原因，尽管经过多年的研究，我们对人类宿主和结核分枝杆菌之间复杂的相互作用的了解仍然不完整，特别是在感染早期发生的事件。人们对细菌和宿主知之甚少，主要是因为它们在临床上是沉默的，然而，我们在非人类灵长类结核病模型中的数据表明，早期事件对于最终结果至关重要并具有预测作用。最近的研究表明，人类微生物组在影响和塑造免疫反应和宿主对感染的结果以及肥胖、心脏病和慢性阻塞性肺病等其他疾病方面发挥着关键作用，尽管大多数研究都集中在肠道上。微生物组，最近肺部微生物组已成为研究的丰富领域，迄今为止，关于结核分枝杆菌感染与肺部微生物组之间是否存在显着相互作用的数据很少。在本提案中，我们将使用非人类灵长类动物。的模型结核分枝杆菌感染忠实地概括了人类结核病的各个方面，以调查结核分枝杆菌感染对肺部微生物组引起的变化，该项目将全面评估这种感染是否会改变猕猴的肺部微生物组，包括改变的程度。我们将首先在感染之前和整个过程中收集系列气道样本，并分析这些样本的微生物组，以使用 PET/CT 成像技术来评估系列进展。感染的情况下，我们将微生物组变化的程度和持续时间与肺部炎症联系起来。该项目将为开始解决肺部微生物组和结核分枝杆菌之间的动态关系提供一个独特的机会，并为未来的研究奠定框架。评估肺微生物组对结核分枝杆菌感染的易感性、免疫反应和感染结果的重要性。该项目代表了复制人类结核病模型中结核病研究的新方向，并且是具有专业知识的实验室之间的合作。结核病猕猴模型以及肺微生物组分类学特征方面的专业知识。