Genetic-based susceptibility to pulmonary tuberculosis

肺结核的遗传易感性

• 批准号: 8807082
• 负责人: GILLIAN L BEAMER
• 金额: $ 26.33万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-15 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8807082
• 关键词: Aerosols; Analysis of Variance; Antibiotic Resistance; Antibiotics; Bacillus (bacterium); Biological; Body Weight; Candidate Disease Gene; Cause of Death; Cessation of life; Chromosome Mapping; Classification; Complex; Computational algorithm; Computer Simulation; Computer software; Data; Data Set; Disease; Environmental Risk Factor; Experimental Models; Foundations; Future; Genes; Genetic; Genetic Variation; Genotype; Goals; Granuloma; Graph; Histologic; Human; Image; Immune; Immune response; Immunity; Inbreeding; Infection; Knowledge; Laboratory mice; Light; Location; Lung; Lymphocyte; Maps; Microscopic; Microscopy; Mining; Modeling; Molecular Genetics; Morbidity - disease rate; Mouse Strains; Mus; Mycobacterium tuberculosis; Necrosis; Neutrophil Infiltration; Newly Diagnosed; Outcome; Pathologic; Pathologist; Pathway interactions; Pattern; Phenotype; Population; Population Heterogeneity; Predisposition; Prevention; Process; Pulmonary Tuberculosis; Research; Resolution; Source; Susceptibility Gene; System; Techniques; Testing; Texture; Therapeutic; Tuberculosis; Vaccination; Validation; Virulent; Work; bacterial genetics; base; improved; innovation; killings; macrophage; mortality; multidisciplinary; neutrophil; novel; pathogen; public health relevance; pulmonary granuloma; response; time use; trait; transmission process; tuberculosis granuloma

 DESCRIPTION (provided by applicant): Tuberculosis (TB), the disease due to Mycobacterium tuberculosis (M.tb) is the leading cause of death due to a single pathogen, killing 1-2 million and newly diagnosed in 8-9 million people each year. By far, the most common form of TB develops in the lungs. Pulmonary TB occurs in the face of intact host immunity and has distinctive pathologic phenotypic traits including granuloma necrosis, neutrophil influx, and cavitation. Here, for the first time, we use Diversity Outbred (DO) mice, to help understand how host genetics influence pulmonary TB. We hypothesize that granuloma-specific phenotypes of pulmonary TB reflect pathways of genetic control. We use an innovative multidisciplinary systems approach to capture, quantify, and analyze biologically relevant disease features of pulmonary TB. The results from this proposal will yield novel information regarding pulmonary TB in genetically diverse populations. Results from these studies will also provide the foundation for future, more extensive work determining predictive signatures of disease, therapeutic, and vaccination responses.