肺结核病严重威胁我国人口健康和经济社会建设。其典型病理特征是由结核菌感染肺脏引起的炎性细胞的局限性浸润和增生所形成的结节状病灶，但目前对肺部肉芽肿的形成及命运调控机制的研究仍非常有限。我们前期研究发现临床肺结核病人的肉芽肿中丝氨酸显著富集。丝氨酸能显著促进结核菌在巨噬细胞中的存活并促进巨噬细胞的死亡。另外，丝氨酸在斑马鱼上显著促进肉芽肿的形成及局部病理损伤。本项目将进一步利用单细胞转录组测序分析临床结核样本、小鼠及斑马鱼模型中肉芽肿的免疫细胞亚群发育和命运转归特征，并研究这些细胞的功能。同时利用蛋白组学、代谢组学、深度测序分析肺部肉芽肿形成过程中的关键通路和分子，并明确这些通路和分子对肺部肉芽肿特异免疫细胞亚群的功能的影响及调控机制。研究结果将加深对结核菌性肉芽肿形成的肺部区域免疫特征及调控机制的了解，同时还将为提高结核病诊疗和治疗性疫苗研发提供可能，具有十分重要的理论意义和实际应用意义。

Tuberculosis (TB) is a serious threat for population health and community economy in our country. The typical pathological hallmark of tuberculosis is granuloma, which is caused by MTB infection-induced leukocyte infiltration and hyperplasia. However, the regulatory mechanisms underlying the formation and fate of granuloma is very limited.In our previous study, we found that serine is significantly upregulated in granuloma of TB patients. Serine promotes survival of MTB and cell apoptosis in macrophages. Furthermore, serine promotes granuloma formation in the model of Zebrafish. In this study, we will investigate immune cell population and development in granuloma formation using single-cell RNA-seq technology. Furthermore, we will identify critical molecular and metabolic pathways with proteomics and metabolomic profiling. The results will deepen our understanding of the immune characteristics and mechanisms of lung granuloma formation during TB infection, and provide important information of TB diagnosis and therapy.