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（由适用提供）：结核病仍然是全球发病率和死亡率的主要原因。尽管进行了多年的研究，但我们对人宿主与结核分枝杆菌之间复杂相互作用的理解仍然不完整。特别是，由于临床沉默的性质，细菌和宿主之间感染早期发生的事件的理解很少。但是，我们在非人类私人结核病模型中的数据表明，早期事件是感染事件结果的至关重要和预测。最近的研究已经实施了人类微生物组，是在影响和塑造感染以及其他疾病（包括肥胖，心脏病和COPD）中的免疫增强和宿主结局中发挥关键作用。尽管大多数研究都集中在肠道微生物组上，但最近，肺微生物组一直是研究丰富的领域。迄今为止，几乎没有关于结核分枝杆菌感染和肺微生物组之间是否存在显着相互作用的数据。在该提案中，我们将使用非人类结核分枝杆菌感染的非人类私人模型，该模型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微生物组引起的变化。该项目将彻底评估该感染是否改变猕猴中的肺微生物组，包括变化的幅度和持续时间。我们最初将在感染之前和整个感染之前收集串行气道样品，然后分析这些样品的微生物组以解决这些问题。使用PET/CT成像技术评估感染的序列进展，我们将将微生物组的变化幅度和变化持续时间与肺部的炎症相关联。该项目将提供一个独特的机会，开始解决肺微生物组和结核分枝杆菌之间的动态，并将为未来的研究奠定框架，以评估肺微生物组对结核分枝杆菌感染的易感性，免疫调查和感染结果的重要性。该项目在复制人类结核病的模型中代表了结核病研究的新方向，并且是在猕猴模型中具有专业知识的实验室之间的合作，以及在肺微生物组的分类表征方面具有专业知识的实验室。