Genetic-based susceptibility to pulmonary tuberculosis

 描述（由申请人提供）：结核病（TB），由结核分枝杆菌（M.tb）引起的疾病，是单一病原体导致死亡的主要原因，造成1-2百万人死亡， 每年有800万到900万人被确诊。到目前为止，结核病最常见的形式是在肺部发展。肺结核发生在面对完整的宿主免疫，并具有独特的病理表型特征，包括肉芽肿坏死，中性粒细胞流入，和空洞。在这里，我们第一次使用多样性远交（DO）小鼠，以帮助了解宿主遗传学如何影响肺结核。我们假设肺结核的肉芽肿特异性表型反映了遗传控制的途径。我们使用创新的多学科系统方法来捕获，量化和分析肺结核的生物学相关疾病特征。这项建议的结果将产生关于遗传多样性人群中肺结核的新信息。这些研究的结果也将为未来更广泛的工作提供基础，确定疾病，治疗和疫苗接种反应的预测特征。

 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.