TREM2通过调控巨噬细胞极化在肺结核病中的作用及分子机制研究

Triggering receptor expressed on myeloid cells 2 mediates the involvement of M2-type macrophages in pulmonary tuberculosis infection

目的探讨肺结核患者肺病灶组织中髓系细胞触发受体2(TREM2)的表达水平,以及与巨噬细胞极化相关标志物的相关性。方法通过苏木素-伊红(H&E)染色评估病理炎症表现,采用免疫组织化学方法检测肺组织中CD68+巨噬细胞和M1/M2巨噬细胞特异性分子及TREM2的表达定位情况,采用酶联免疫吸附试验(ELISA)和实时荧光定量PCR(qRT-PCR)检测外周血中M1/M2巨噬细胞相关细胞因子IL-10和IL-12的表达水平,并进一步分析TREM2与M1/M2巨噬细胞特征细胞因子的相关性。结果肺结核患者病灶组织中有明显的朗汉斯巨细胞和结核性肉芽肿。TREM2和巨噬细胞极化相关标志物在肉芽肿周围的表达均显著增加,且TREM2和M2巨噬细胞标志物CD163的表达定位一致。肺结核患者外周血中TREM2、IL-10和IL-12的mRNA表达水平以及IL-10、IL-12的表达量显著高于对照组。相关性分析表明TREM2与M2巨噬细胞相关细胞因子IL-10呈显著正相关。结论TREM2与M2巨噬细胞特异性细胞因子呈正相关,提示TREM2可能介导巨噬细胞向M2极化在肺结核的发生发展过程中发挥关键作用。

Objective To investigate the expression level of myeloid triggered receptor 2(TREM2)in lung lesion tissues of patients with tuberculosis and its correlation with markers related to macrophage polarization.Methods The pathological inflammatory manifestations were assessed by hematoxylin-eosin(H&E)staining,the expression and localization of CD68+macrophages and M1/M2macrophage-specific molecules and TREM2in lung tissues were detected by immunohistochemistry,and the expression levels of M1/M2macrophage-associated cytokines IL-10and IL-12were examined in peripheral blood by using enzyme-linked immunosorbent assay(ELISA)and real-time fluorescence quantitative PCR(qRT-PCR),and the correlation between TREM2 and the characteristic cytokines of M1/M2 macrophages was further analyzed.Results Patients with pulmonary tuberculosis had significant Langhans giant cells and tuberculous granulomas in the focal tissues.The expression of both TREM2and macrophage polarization-associated markers was significantly increased around the granulomas,and the expression of TREM2and the M2 macrophage marker,CD163,were localized in the same way.The mRNA expression levels of TREM2,IL-10and IL-12as well as the expression of IL-10and IL-12in the peripheral blood of patients with pulmonary tuberculosis were significantly higher than those of controls.Correlation analysis showed a significant positive correlation between TREM2and the M2 macrophage-associated cytokine IL-10.Conclusion TREM2was positively correlated with M2 macrophage-specific cytokines,suggesting that TREM2may mediate the critical role of macrophage polarization to M2in the development of TB.