新疆地区耐多药与药物敏感肺结核患者外周血转录组学差异及免疫浸润特征分析

doi:10.19871/j.cnki.xfcrbzz.2026.01.003

新发传染病电子杂志 ›› 2026, Vol. 11 ›› Issue (1): 23-27.doi: 10.19871/j.cnki.xfcrbzz.2026.01.003

新疆地区耐多药与药物敏感肺结核患者外周血转录组学差异及免疫浸润特征分析

徐亮亮¹, 刘欣², 杨婷³, 张君⁴, 陈志祥⁵, 关小军¹, 郑甜⁶

1.新疆维吾尔自治区第六人民医院胸外一科,新疆乌鲁木齐 830013;
2.新疆维吾尔自治区第六人民医院临床营养科,新疆乌鲁木齐 830013;
3.新疆维吾尔自治区第六人民医院检验科,新疆乌鲁木齐 830013;
4.新疆维吾尔自治区第六人民医院结核二科,新疆乌鲁木齐 830013;
5.新疆维吾尔自治区第六人民医院胸外二科,新疆乌鲁木齐 830013;
6.新疆维吾尔自治区第六人民医院教科办,新疆乌鲁木齐 830013

收稿日期:2025-09-12 出版日期:2026-02-28 发布日期:2026-03-16
通讯作者: 郑甜,Email：490823460@qq.com
基金资助:
1.省部共建中亚高发病成因与防治国家重点实验室联合基金项目（SKL-HIDCA-2024-BF5）2.新疆维吾尔自治区第六人民医院2020年度院级科研项目（202004）

Transcriptomic differences and immune infiltration characteristics in peripheral blood of multidrug-resistant and drug-sensitive pulmonary tuberculosis patients in Xinjiang

Xu Liangliang¹, Liu Xin², Yang Ting³, Zhang Jun⁴, Chen Zhixiang⁵, Guan Xiaojun¹, Zheng Tian⁶

1. Department of Thoracic Surgery, the Sixth People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Urumqi 830013, China;
2. Department of Clinical Nutrition, the Sixth People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Urumqi 830013, China;
3. Department of Laboratory Medicine, the Sixth People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Urumqi 830013, China;
4. Department of Tuberculosis Ⅱ, the Sixth People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Urumqi 830013, China;
5. Department of Thoracic Surgery II, the Sixth People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Urumqi 830013, China;
6. Education and Science Office, the Sixth People's Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Urumqi 830013, China

Received:2025-09-12 Online:2026-02-28 Published:2026-03-16

摘要/Abstract

摘要： 目的分析耐多药与药物敏感肺结核患者的外周血转录组学差异及免疫浸润特征、并探讨差异基因表达水平与免疫细胞占比的关联性,为耐多药肺结核的发病机制解析提供依据。方法本研究为横断面研究,选取2024年1月至12月在新疆维吾尔自治区第六人民医院就诊的10例肺结核患者为研究对象,根据分子药敏结果分为耐多药组（n=5）和药物敏感组（n=5）。收集10例患者静脉血全血样本并提取RNA进行高通量测序,通过mRNA转录组学分析获得两组中的差异基因。采用基因本体论（gene ontology,GO）和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes,KEGG）数据库,对差异基因进行功能注释及通路富集分析,以明确其关联功能与核心富集通路。基于quantiseq算法计算样本的免疫细胞组成并比较免疫细胞占比在两组间的差异。挑选免疫相关差异基因,采用Spearman相关分析计算该类基因与上述免疫细胞占比之间的相关性。结果研究以药物敏感肺结核患者为对照,基于既定的差异基因筛选阈值,在耐多药肺结核患者中共筛选出583个差异表达基因,其中上调基因330个、下调基因253个。10种免疫细胞中,耐多药肺结核患者中性粒细胞占比显著高于药物敏感肺结核患者（P<0.05）。共7个免疫相关差异基因的表达值与中性粒细胞占比具有较强的相关性（|R|>0.5）,其中MAP1LC3A和CASP5的表达水平与中性粒细胞占比的相关性最强。MAP1LC3A的表达水平与中性粒细胞占比呈负相关（R=-0.527,P=0.117）,而CASP5的表达水平与中性粒细胞占比呈正相关（R=0.661,P=0.038）。结论与药物敏感肺结核患者相比,耐多药肺结核患者的外周血中性粒细胞占比显著增加。耐多药肺结核患者外周血的MAP1LC3A表达水平下调和CASP5表达水平上调与中性粒细胞占比增加高度相关。由MAP1LC3A介导的自噬机制和以CASP5为主的中性粒细胞胞外杀菌网络生成及炎症反应异常或是深入探究肺结核耐药机制的重要突破口。

关键词: 肺结核, 耐多药, 转录组测序, 免疫微环境

Abstract: Objective To analyze the differences in peripheral blood transcriptomics and immune infiltration characteristics between multidrug-resistant tuberculosis (MDR-TB) and drug-susceptible tuberculosis (DS-TB) patients, explore the correlation between differential gene expression levels and immune cell proportions, and provide evidence for elucidating the pathogenesis of MDR-TB. Method This cross-sectional study enrolled 10 pulmonary tuberculosis patients who admitted to Sixth People's Hospital of Xinjiang Uygur Autonomous Region from January to December 2024. Based on molecular drug sensitivity results, they were divided into a multidrug-resistant group and a drug-sensitive group. Venous whole blood samples were collected from each patients, and RNA was extracted for high-throughput sequencing. Differentially expressed genes in the two groups were identified through mRNA transcriptomics analysis. The gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases were used to perform functional annotation and pathway enrichment analysis on the differentially expressed genes to clarify their associated functions and core enriched pathways. The immune cell composition of the patients was calculated using the quantexq algorithm, and the differences in immune cell percentage between the two groups were compared. Immune-related differentially expressed genes were selected, and Spearman correlation analysis was used to calculate the correlation between these genes and the immune cell percentages. Result Using drug-sensitive pulmonary tuberculosis patients as the control and based on the predefined screening thresholds for differentially expressed genes, a total of 583 differentially expressed genes were identified in multidrug-resistant pulmonary tuberculosis patients, including 330 upregulated genes and 253 downregulated genes. Among the 10 immune cell types, the percentage of neutrophils in multidrug-resistant group was significantly higher than that in drug-sensitive tuberculosis group (P<0.05). The expression levels of seven immune-related differentially expressed genes showed a strong correlation with the percentage of neutrophils (|R|>0.5), with MAP1LC3A and CASP5 showing the strongest correlation. Specifically, the expression level of MAP1LC3A was negatively correlated with the proportion of neutrophils (R=-0.527, P=0.117), while the expression level of CASP5 was positively correlated with the proportion of neutrophils (R=0.661, P=0.038). Conclusion Compared with drug-sensitive patients, multidrug-resistant tuberculosis patients had a significantly increased percentage of peripheral blood neutrophils. Downregulation of MAP1LC3A and upregulation of CASP5 in the peripheral blood of multidrug-resistant tuberculosis patients were highly correlated with the increased percentage of neutrophils.The autophagy mechanism mediated by MAP1LC3A and the abnormal neutrophil extracellular traps generation and inflammatory response mainly based on CASP5 were important breakthroughs for in-depth research into the drug resistance mechanism of pulmonary tuberculosis.

Key words: Pulmonary tuberculosis, Multidrug-resistant, Transcriptomics, Immune microenvironment

中图分类号:

R521

徐亮亮, 刘欣, 杨婷, 张君, 陈志祥, 关小军, 郑甜. 新疆地区耐多药与药物敏感肺结核患者外周血转录组学差异及免疫浸润特征分析[J]. 新发传染病电子杂志, 2026, 11(1): 23-27.

Xu Liangliang, Liu Xin, Yang Ting, Zhang Jun, Chen Zhixiang, Guan Xiaojun, Zheng Tian. Transcriptomic differences and immune infiltration characteristics in peripheral blood of multidrug-resistant and drug-sensitive pulmonary tuberculosis patients in Xinjiang[J]. Electronic Journal of Emerging Infectious Diseases, 2026, 11(1): 23-27.

参考文献

[1] TRAJMAN A, CAMPBELL JR, KUNOR T, et al.Tuberculosis[J]. Lancet, 2025, 405(10481): 850-866.
[2] world health organization. Global tuberculosis report 2025[R]. Geneva: World Health Organization, 2025.
[3] SU W, RUAN YZ, LI T, et al.Characteristics of rifampicin-resistant tuberculosis detection in China, 2015-2019[J]. Infect Dis Poverty, 2021, 10(1): 99.
[4] BOBBA S, KHADER SA.Rifampicin drug resistance and host immunity in tuberculosis: more than meets the eye. Trends Immunol. 2023, 44(9): 712-723.
[5] LYU MY, LAI HL, PENG HR, et al.Immunotherapy for tuberculosis: current strategies and future directions[J]. Mil Med Res, 2025, 12(1): 68.
[6] SONG F, QIAN Y, PENG X, et al.The frontline of immune response in peripheral blood[J]. PLoS One, 2017, 12(8): e0182294.
[7] 谢蓝田, 阮桂仁, 刘晓清,等. 212例活动性结核病患者外周血淋巴细胞亚群特点:单中心描述性研究[J]. 协和医学杂志, 2023, 14(1): 131-138.
[8] 中华人民共和国国家卫生和计划生育委员会. 肺结核诊断标准(WS 288-2017)[J/CD]. 新发传染病电子杂志, 2018, 3(1): 59-61.
[9] 中华人民共和国国家卫生和计划生育委员会. 结核病分类(WS196-2017)[S]. 2017.
[10] ZENG D, YE Z, SHEN R, et al.IOBR: Multi-Omics Immuno-Oncology Biological Research to Decode Tumor Microenvironment and Signatures[J]. Front Immunol, 2021, 12: 687975.
[11] FINOTELLO F, MAYER C, PLATTNER C, et al.Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data[J]. Genome Med, 2019, 11(1): 34.
[12] BORKUTE RR, WOELKE S, PEI G, et al.Neutrophils in Tuberculosis: Cell Biology, Cellular Networking and Multitasking in Host Defense[J]. Int J Mol Sci, 2021, 22(9): 4801.
[13] PELLEGRINI JM, SABBIONE F, MORELLI MP, et al.Neutrophil autophagy during human active tuberculosis is modulated by SLAMF1[J]. Autophagy, 2021, 17(9) :2629-2638.
[14] FILIO-RODRÍGUEZ G, ESTRADA-GARCÍA I, ARCE-PAREDES P, et al. In vivo induction of neutrophil extracellular traps by Mycobacterium tuberculosis in a guinea pig model[J]. Innate Immun, 2017, 23(7): 625-637.
[15] BRAIAN C, HOGEA V, STENDAHL O.Mycobacterium tuberculosis- induced neutrophil extracellular traps activate human macrophages[J]. J Innate Immun, 2013, 5(6): 591-602.
[16] SOLLBERGER G, CHOIDAS A, BURN GL, et al. Gasdermin D plays a vital role in the generation of neutrophil extracellular traps[J]. Sci Immunol, 2018, 3(26): eaar6689.

新疆地区耐多药与药物敏感肺结核患者外周血转录组学差异及免疫浸润特征分析

Transcriptomic differences and immune infiltration characteristics in peripheral blood of multidrug-resistant and drug-sensitive pulmonary tuberculosis patients in Xinjiang

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