Wu Yi-Lin, Li Yuan-Ting, Liu Gan-Bin, Wu Jin-Lin, Liu Xiao-Ran, Gao Xin-Xuan, Huang Qi-Dan, Liang Jin, Ouyang Jia-Yi, Ding Yi-Ran, Wu Jun-Yi, Lu Yuan-Bin, Gao Yu-Chi, Cai Xiao-Zhen, Zhang Jun-Ai
Department of Cardiology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, China.
Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, School of Medical Technology, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China.
Proteome Sci. 2024 Dec 4;22(1):13. doi: 10.1186/s12953-024-00235-y.
Tuberculosis drug resistance contributes to the spread of tuberculosis. Immunotherapy is an effective strategy for treating tuberculosis, with the regulation of macrophage-mediated anti-tuberculosis immunity being crucial. Norcantharidin (NCTD), a drug used in tumor immunotherapy, has significant immunomodulatory effects. Thus, NCTD may have an anti-tuberculosis role by regulating immunity. Understanding how NCTD affects the proteome of Mtb-infected macrophages can provide valuable insights into potential treatments. This study aimed to investigate the impact of NCTD (10 μg/mL) on the proteome of macrophages infected with Mtb H37Ra using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. A total of 69 differentially regulated proteins (DRPs) were identified, with 28 up-regulated and 41 down-regulated in the NCTD-treated group. Validation of six DRPs (CLTCL1, VAV1, SP1, TRIM24, MYO1G, and WDR70) by Western blot analysis confirmed the accuracy of the LC-MS/MS method used in this study. NCTD modulates various protein expressions involved in chromatin-modifying enzymes, RHO GTPases activating PAKs, Fc gamma R-mediated phagocytosis, T cell receptor signaling pathway, and antigen processing and presentation. Overall, the research provides new insights into the effects of NCTD on the proteome of Mtb-infected macrophages. The identified changes highlight potential targets for future therapeutic interventions aimed at enhancing host immunity against Mtb infection or developing new anti-TB drugs based on these findings.
结核耐药性促使结核病传播。免疫疗法是治疗结核病的有效策略，其中调节巨噬细胞介导的抗结核免疫至关重要。去甲斑蝥素（NCTD）是一种用于肿瘤免疫疗法的药物，具有显著的免疫调节作用。因此，NCTD可能通过调节免疫发挥抗结核作用。了解NCTD如何影响感染结核分枝杆菌的巨噬细胞的蛋白质组，可为潜在治疗提供有价值的见解。本研究旨在使用液相色谱-串联质谱（LC-MS/MS）分析，研究NCTD（10μg/mL）对感染结核分枝杆菌H37Ra的巨噬细胞蛋白质组的影响。共鉴定出69种差异调节蛋白（DRP），在NCTD处理组中，有28种上调，41种下调。通过蛋白质印迹分析对6种DRP（CLTCL1、VAV1、SP1、TRIM24、MYO1G和WDR70）进行验证，证实了本研究中使用的LC-MS/MS方法的准确性。NCTD调节参与染色质修饰酶、激活PAKs的RHO GTPases、FcγR介导的吞噬作用、T细胞受体信号通路以及抗原加工和呈递的各种蛋白质表达。总体而言，该研究为NCTD对感染结核分枝杆菌的巨噬细胞蛋白质组的影响提供了新见解。所确定的变化突出了未来治疗干预的潜在靶点，旨在增强宿主对结核分枝杆菌感染免疫或基于这些发现开发新的抗结核药物。
