Tuberculosis infection activates the autoimmune system. However, the role of host-pathogen interactions involved in Mycobacterium tuberculosis infection is unclear. In this study, we analyzed 6 spinal tuberculosis tissues and 6 herniated disc tissues by using liquid chromatography-tandem mass spectrometry coupled with tandem mass spectrometry, and immunohistochemical staining was performed for validating the results. We identified 42 differential immune-related proteins and 3 hub genes that are primarily localised in the tertiary granule and involved in biological processes such as cellular response to the presence of cadmium ions, regulation of ion transmembrane transport, transmembrane transport, and inflammatory responses. Genes encoding cytochrome B-245 beta chain (CYBB), matrix metallopeptidase 9 (MMP9), and C-X-C motif chemokine ligand 10 (CXCL10) were identified as the hub genes that exhibited anti-tuberculosis activity and were responsible for macrophage resistance against M. tuberculosis. In conclusion, CYBB, MMP9, and CXCL10 resist M. tuberculosis infection through chemotaxis and macrophage activation. Our results indicate that CYBB, MMP9, and CXCL10 could be considered as molecular targets for spinal tuberculosis treatment, which may significantly improve patients' quality of life and prognosis.

中文翻译：

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蛋白质组学分析揭示了参与巨噬细胞抗脊柱结核过程的关键分子机制

结核病感染会激活自身免疫系统。然而，宿主-病原体相互作用在结核分枝杆菌感染中的作用尚不清楚。在本研究中，我们使用液相色谱-串联质谱联用串联质谱法分析了 6 个脊柱结核组织和 6 个椎间盘突出组织，并进行了免疫组织化学染色以验证结果。我们鉴定了 42 种差异免疫相关蛋白和 3 个中枢基因，它们主要位于三级颗粒中并参与生物过程，例如对镉离子存在的细胞反应、离子跨膜转运的调节、跨膜转运和炎症反应。编码细胞色素 B-245 β 链 (CYBB)、基质金属肽酶 9 (MMP9)、和 CXC 基序趋化因子配体 10 (CXCL10) 被鉴定为具有抗结核活性并负责巨噬细胞对结核分枝杆菌的抗性的中枢基因。总之，CYBB、MMP9 和 CXCL10 通过趋化性和巨噬细胞激活抵抗结核分枝杆菌感染。我们的研究结果表明，CYBB、MMP9 和 CXCL10 可作为脊柱结核治疗的分子靶点，可显着改善患者的生活质量和预后。