非结核分枝杆菌感染对非小细胞肺癌巨噬细胞吞噬功能及CD_(4)^(+)T细胞亚群的影响

Influence of non-tuberculous Mycobacteria infection on macrophage phagocytosis and CD_(4)^(+) T cell subsets in patients with non-small cell lung cancer

目的 研究非结核分枝杆菌(NTM)感染对非小细胞肺癌(NSCLC)巨噬细胞吞噬功能及CD_(4)^(+)T细胞亚群的影响。方法 选取2019年2月-2022年1月于福建医科大学附属闽东医院就诊的NSCLC患者100例和健康体检者50名为研究对象,根据NSCLC患者是否感染NTM分为未感染组50例和感染组50例,检测感染组病原菌类型,比较三组研究对象巨噬细胞吞噬水平,并检测血清CD_(4)^(+)T淋巴细胞转录因子T盒子21转录因子(T-bet)、GATA结合蛋白3(GATA3)、维甲酸孤儿核受体γt(ROR-γt)、叉头样转录因子P3(FOXP3)与特异细胞因子干扰素γ(IFN-γ)、白细胞介素(IL)-4、IL-17。结果 感染组患者炎性细胞总数高于健康组,低于未感染组,巨噬细胞占比和吞噬指数(PI)低于未感染组和健康组(P<0.05);感染组痰液巨噬细胞Beclin-1、LC3-I、LC3-II mRNA及蛋白表达水平高于健康组,低于未感染组(P<0.05);未感染组和感染组血清T-bet、GATA3、ROR-γt、FOXP3的RNA表达及IFN-γ、IL-4、IL-17、FOXP3蛋白相对表达量高于健康组(P<0.05);与未感染组比较,感染组血清中T-bet的RNA表达及IFN-γ的蛋白相对表达量低,GATA3、ROR-γt、FOXP3的RNA表达及IL-4、IL-17、FOXP3蛋白相对表达量升高(P<0.05)。结论 非结核分枝杆菌感染对非小细胞肺癌患者巨噬细胞的吞噬功能有抑制作用,对CD_(4)^(+)T细胞亚群的分化有促进作用。

OBJECTIVE To observe the influence of non-tuberculous Mycobacteria(NTM) infection on macrophage phagocytosis and CD_(4)^(+)T cell subsets in patients with non-small cell lung cancer(NSCLC). METHODS Totally 100 NSCLC patients who were treated in Mindong Hospital, Fujian Medical University from Feb 2019 to Jan 2022 were recruited as the research subjects, meanwhile, 50 healthy people who received physical examination were also recruited as the research subjects. The NSCLC patients were divided into the infection group with 50 cases and the no infection group with 50 cases according to the status of infection. The species of pathogens were detected, the levels of macrophage phagocytosis were compared among the three groups of research subjects. The levels of serum CD_(4)^(+)T cell transcription factor T-box 21 transcription factor(T-bet), GATA-binding protein 3(GATA3), retinoic acid orphan nuclear receptor γt(ROR-γt), forkhead box P3(FOXP3), specific cytokines interferon-γ(IFN-γ), interleukin(IL)-4 and IL-17 were detected. RESULTS The total counts of inflammatory cells of the infection group were higher than those of the healthy group and the no infection group, the percentage of macrophage and phago cyticindex(PI) of the infection group were lower than those of the no infection group and the health group(P<0.05). The expression levels of macrophage Beclin-1, LC3-I, LC3-II mRNA and proteins in sputum were higher in the infection group than in the healthy group, which were lower in the infection group than in the no infection group(P<0.05). The expression levels of serum T-bet, GATA3, ROR-γt and FOXP3 RNA as well as relative expression levels of IFN-γ, IL-4, IL-17 and FOXP3 proteins were higher in the no infection group and the infection group than in the healthy group(P<0.05). The expression level of serum T-bet RNA and relative expression level of IFN-γ protein were lower in the infection group than in the no infection group, while the expression levels of GATA3, ROR-γt and FOXP3 RNA as well as relative expression levels of IL-4, IL-7 and FOXP3 were higher in the infection group than in the no infection group(P<0.05). CONCLUSION The NTM infection may inhibit the macrophage phagocytosis and promote the differentiation of CD_(4)^(+)T cell subsets.