盖尔森基兴诺卡菌GUH-2感染小鼠后细胞因子分泌特征研究

Secretion characteristics of cytokines in mice after infected with Nocardia cyriaciorgica GUH-2

目的了解盖尔森基兴诺卡菌感染小鼠后细胞因子的分泌特征,进一步阐明其致病机制,为诺卡菌病的治疗提供理论基础。方法滴鼻感染BALB/c小鼠,采用平板计数法统计不同时间点小鼠肺上清及血清中的菌载量。采用酶联免疫吸附试验(ELISA)检测在不同时间点肺上清及血清中多种细胞因子的浓度。采用SPSS 23.0软件进行统计学分析。结果小鼠感染48 h后,98.35%的肺内盖尔森基兴诺卡菌被清除,在血清中没有检测到该菌。在感染早期,肺组织中IL-2、IL-4、IL-6、IL-10、IL-12、TNF-α、IFN-γ的浓度均明显高于对照组,差异有统计学意义(P<0.01),随着时间的推移,各细胞因子的浓度呈现逐渐下降的趋势。在血清中,IL-6(6~24 h)、IFN-γ(12~24 h)与IL-10(48 h)浓度较高,与对照组相比差异有统计学意义(P<0.01)。IL-12(12~48 h)与IL-4(12 h)的表达受到抑制,与对照组相比差异有统计学意义(P<0.01)。另外,在肺中,各细胞因子的浓度与菌载量之间符合线性相关,且均呈正相关。结论在小鼠感染盖尔森基兴诺卡菌的过程中,机体会分泌IL-6、TNF-α、IL-12、IL-2、IFN-γ、IL-10、IL-4等细胞因子,尤其是IL-6、IL-12、IFN-γ和IL-10浓度较高。各细胞因子交互作用参与了清除盖尔森基兴诺卡菌感染的免疫效应机制。

Objective To understand the characteristics of cytokine secretion in mice after infected with Nocardia cyriacigeorgica, clarify its pathogenesis, and provide theoretical basis for the treatment of nocardiosis. Methods BALB/c mice were infected by nasal drip, and then the bacterial loads in the lung of the mice at different time intervals were counted by plate counting. Enzyme linked immunosorbent assay(ELISA) was used to detect the concentration of cytokines in lung tissues and serum of the mice at different time intervals. Software SPSS 23.0 was used for statistical analysis. Results Most of N. cyriacigeorgica(98.35%) in the lung tissues of the mice were eliminated at 48 h after infection, and no N. cyriacigeorgica was detected in serum of the mice. In the early stage of infection, the concentrations of IL-2, IL-4, IL-6, IL-10, IL-12, TNF-αand IFN-γ in the lung tissues of the mice were significantly higher than those in the control group(P<0.01). The concentrations of these cytokines showed a trend of decline over time. In serum of the mice, the concentrations of IL-6(6–24 h),IFN-γ(12–24 h) and IL-10(48 h) were higher than those in the control group. The difference was significant(P<0.01). And the concentrations of IL-12(12–48 h) and IL-4(12 h) were significantly inhibited compared with the control group. The difference was significant(P<0.01). In addition, there were positive correlations between the concentrations of cytokines and bacterial loads in the lung tissues of the mice. Conclusion In the process of infection with N. cyriacigeorgica in mice,cytokines such as IL-6, TNF-α, IL-12, IL-2, IFN-γ, IL-10, IL-4 were secreted, especially the high concentrations of IL-6,IL-12, IFN-γ and IL-10. The interactions of various cytokines were involved in the immune response mechanism of eliminating N. cyriacigeorgica infection.