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.