腺病毒肺炎患儿cGAS/STING基因表达与树突状细胞含量及成熟标志物变化在疾病免疫应答中的研究

Study on cGAS/STING gene expression,dendritic cell composition,and maturation markers in the immune response of children with adenovirus pneumonia

为探讨腺病毒肺炎急性期患儿干扰素基因刺激因子(stimulator of interferon gene,STING)、环腺苷酸鸟苷酸合成酶(cyclic GMP AMP synthase,cGAS)mRNA表达及髓样树突状细胞(myeloid dendritic cell,mDC)数量、表面成熟标志物CD80和CD86的变化、相关细胞因子的情况,及各指标间的相关性,分析腺病毒肺炎感染后机体的免疫应答反应,选取腺病毒肺炎急性期患儿34例,健康对照组34例,应用qRT-PCR检测单个核细胞STING、cGAS mRNA相对表达量;ELISA检测血清IFN-α、IFN-β、TNF-α、IL-6含量;FACS检测单个核细胞mDC数量及表面标志物CD80、CD86的变化,分析各指标之间的相关性。结果显示,与对照组比较,腺病毒肺炎组STING、cGAS mRNA表达增加,IFN-α、IFN-β、TNF-α、IL-6水平升高,mDC增加,CD80、CD86水平升高(P<0.05)。mDC与STING mRNA、cGAS mRNA、IFN-α、TNF-α、IL-6呈正相关;CD80与STING mRNA、cGAS mRNA、IFN-α、IFN-β、TNF-α、IL-6呈正相关;CD86与IFN-α、IFN-β、TNF-α呈正相关(P<0.05)。该研究提示,腺病毒肺炎患儿高表达STING/cGAS基因,存在mDC增加及成熟、IFN-α等细胞因子分泌增加等免疫变化,可能进一步激活cGAS-STING通路,介导固有免疫而发挥其抗病毒作用。

This study aims to investigate the changes in mRNA expressions of stimulator of interferon gene(STING)and cyclic GMP AMP synthase(cGAS),the composition of myeloid dendritic cells(mDC)and their surface maturation markersCD80 and CD86,the related cytokines,and the correlation among above indicators to analyze the immune response upon adenovirus pneumonia infection.34 children with acute stage adenovirus pneumonia and 34 healthy children were included in the study.The relative mRNA expression levels of STING and cGAS in the peripheral mononuclear cells were detected by qRT-PCR.The levels of IFN-α,IFN-β,TNF-α,and IL-6 were detected by ELISA.FACS was used to detect the mDC composition and surface markers CD80 and CD86.The correlation of the above indicators was analyzed.The results showed that compared to those of the control group,mRNA expression levels of STING and cGAS,IFN-α,IFN-β,TNF-α,IL-6,mDC cell number,CD80,and CD86 were all increased in adenovirus pneumonia patients(P<0.05).The level of mDC was positively correlated with the expressions of STING mRNA,cGAS mRNA,IFN-α,TNF-α,and IL-6.The CD80 level was positively correlated with STING mRNA,cGAS mRNA,IFN-α,IFN-β,TNF-α,and IL-6,whereas CD86 was positively correlated with IFN-α,IFN-β,and TNF-α(P<0.05).This study suggests that STING/cGAS genes are highly expressed in children with adenovirus pneumonia who exhibit increased mDC number,maturation markers,and cytokine secretion.The cGAS-STING pathway may be further activated to mediate innate immunity and exert antiviral effect.