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）：结核病仍然是全球发病率和死亡率的主要原因。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相互作用的理解仍然不完整。特别是，细菌和宿主之间感染早期发生的事件知之甚少，主要是由于它们的临床沉默性质。然而，我们在非人灵长类动物结核病模型中的数据表明，早期事件是感染最终结果的关键和预测因素。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其他疾病（包括肥胖症、心脏病和COPD）中发挥着关键作用。虽然大多数研究都集中在肠道微生物组上，但最近肺部微生物组已经成为一个丰富的研究领域。迄今为止，关于M之间是否存在显著的相互作用的数据很少。结核感染和肺部微生物组。在这个提议中，我们将使用M的非人灵长类动物模型。结核感染，忠实地概括了人类结核病的各个方面，调查的变化，M。肺结核感染对肺部微生物组有影响。该项目将彻底评估这种感染是否会改变猕猴的肺部微生物组，包括变化的幅度和持续时间。我们将首先在感染之前和整个感染过程中收集系列气道样本，随后对这些样本的微生物组进行测序和分析，以解决这些问题。使用PET/CT成像技术来评估感染的连续进展，我们将微生物组变化的幅度和持续时间与肺部炎症相关联。该项目将提供一个独特的机会，开始解决肺部微生物组和M.结核病，并将奠定框架，为未来的研究，以评估肺微生物组的重要性，易感性，免疫反应和感染的结果，在M。肺结核感染。该项目代表了复制人类结核病模型的结核病研究的新方向，并且是具有结核病猕猴模型专业知识的实验室和具有肺部微生物组分类学特征的实验室之间的合作。