Zeng Qingqiu, Tong Zhaowei, Zhong Jianfeng, Li Xiaofeng, Shen Bin, Chen Haiyan, Ge Dating
Department of Infectious Diseases, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang, 313000, China.
Department of Infectious Diseases, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang, 313000, China; Huzhou Key Laboratory of Precision Medicine Research and Translation for Infectious Diseases, Huzhou, Zhejiang, 313000, China.
Tuberculosis (Edinb). 2025 May;152:102614. doi: 10.1016/j.tube.2025.102614. Epub 2025 Feb 11.
Most of Mycobacterium tuberculosis(Mtb) infection result in the formation of granulomas, which are often rich in immune cells, with subsequent clinical symptoms. However, the role of the immune system in the formation of tuberculosis granuloma structures has not been fully revealed. Here we first analyzed single-cell transcriptome and microenvironment spatial characteristics to reveal the contribution of immune cells to granuloma expansion with validation by immunofluorescence. We then integrated published peripheral blood transcriptome data for Mtb-infected patients and healthy controls. Immune cell profiles were deconvoluted and results were validated on a local cohort using flow cytometry. At the same time, an in-depth evaluation of the changes in the population and function of multiple peripheral blood immune cells during tuberculosis infection were conducted to define correlation with granuloma area. Finally, we screened 6 cytokines (IL6, IL8, IL10, IFNγ, TNFα, TGFβ) through machine learning bioinformatics and analyzed their correlation with the size of tuberculosis granuloma. Based on these findings, we confirmed that the dynamic variation in proportion of immune cells in peripheral blood and the levels of cytokine profiles are closely related to the occurrence and development of tuberculosis granuloma. This study provides a theoretical basis for the molecular mechanism of tuberculosis granuloma.
大多数结核分枝杆菌（Mtb）感染会导致肉芽肿的形成，这些肉芽肿通常富含免疫细胞，并伴有随后的临床症状。然而，免疫系统在结核肉芽肿结构形成中的作用尚未完全揭示。在此，我们首先分析单细胞转录组和微环境空间特征，以揭示免疫细胞对肉芽肿扩展的贡献，并通过免疫荧光进行验证。然后，我们整合了已发表的Mtb感染患者和健康对照的外周血转录组数据。对免疫细胞图谱进行反卷积分析，并使用流式细胞术在本地队列中对结果进行验证。同时，对结核感染期间多种外周血免疫细胞的数量和功能变化进行深入评估，以确定与肉芽肿面积的相关性。最后，我们通过机器学习生物信息学筛选出6种细胞因子（IL6、IL8、IL10、IFNγ、TNFα、TGFβ），并分析它们与结核肉芽肿大小的相关性。基于这些发现，我们证实外周血免疫细胞比例的动态变化和细胞因子谱水平与结核肉芽肿的发生发展密切相关。本研究为结核肉芽肿的分子机制提供了理论依据。
