The correlation between immune profiles and pathological changes in pulmonary tuberculosis granulomas revealed by bioinformatic analysis and experimental validation

IF 2.8 3区医学 Q3 IMMUNOLOGY

Tuberculosis Pub Date : 2025-02-11 DOI:10.1016/j.tube.2025.102614

Qingqiu Zeng , Zhaowei Tong , Jianfeng Zhong , Xiaofeng Li , Bin Shen , Haiyan Chen , Dating Ge

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引用次数: 0

Abstract

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.

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免疫谱与肺结核肉芽肿病理变化的相关性：生物信息学分析与实验验证

大多数结核分枝杆菌（Mtb）感染导致肉芽肿的形成，肉芽肿通常富含免疫细胞，随后出现临床症状。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。在这里，我们首先分析了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张的贡献，并通过免疫荧光验证。然后，我们整合了已发表的mtb感染患者和健康对照者的外周血转录组数据。免疫细胞谱被反卷积，结果在本地队列中使用流式细胞术进行验证。同时，深入评估结核感染期间多种外周血免疫细胞的数量和功能变化，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了6种细胞因子（IL6、IL8、IL10、IFNγ、TNFα、TGFβ），并分析了它们与结核肉芽肿大小的相关性。基于这些发现，我们证实了外周血免疫细胞比例和细胞因子谱水平的动态变化与结核肉芽肿的发生和发展密切相关。本研究为探讨结核肉芽肿的分子机制提供了理论依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tuberculosis 医学-呼吸系统

CiteScore

4.60

自引率

3.10%

发文量

审稿时长

49 days

期刊介绍： Tuberculosis is a speciality journal focusing on basic experimental research on tuberculosis, notably on bacteriological, immunological and pathogenesis aspects of the disease. The journal publishes original research and reviews on the host response and immunology of tuberculosis and the molecular biology, genetics and physiology of the organism, however discourages submissions with a meta-analytical focus (for example, articles based on searches of published articles in public electronic databases, especially where there is lack of evidence of the personal involvement of authors in the generation of such material). We do not publish Clinical Case-Studies. Areas on which submissions are welcomed include: -Clinical TrialsDiagnostics- Antimicrobial resistance- Immunology- Leprosy- Microbiology, including microbial physiology- Molecular epidemiology- Non-tuberculous Mycobacteria- Pathogenesis- Pathology- Vaccine development. This Journal does not accept case-reports. The resurgence of interest in tuberculosis has accelerated the pace of relevant research and Tuberculosis has grown with it, as the only journal dedicated to experimental biomedical research in tuberculosis.