利什曼原虫感染树突状细胞早期基因表达差异分析及关键基因筛选

Differential analysis of gene expression and screening of key genes in dendritic cells in early stage of infection with Leishmania

目的:分析利什曼原虫感染树突状细胞(DCs)早期的基因表达与信号通路变化,探究DCs感染后应答,寻找利什曼原虫感染后基于DCs的免疫治疗方法。方法:GEO数据库下载利什曼原虫感染前后DCs基因芯片数据,RStudio软件筛选差异表达基因(DEGs),STRING构建DEGs蛋白质相互作用网络(PPI),Cytoscape筛选差异表达蛋白质的核心模块,RStudio软件对DEGs进行GO和KEGG富集分析。结果:共筛选出DEGs 129个,其中IL12B与CXCL10差异最为显著,GO分析共富集23个过程,主要涉及病毒感染过程相关细胞反应及Ⅰ-IFN相关免疫反应;KEGG分析共富集3条信号通路,分别为甲型流感、麻疹及DNA复制信号通路。结论:利什曼原虫感染DCs前后Ⅰ-IFN信号通路和TLR4/NF-κB信号通路激活,影响IL12表达,提示Ⅰ-IFN/IL12信号通路与TLR4/NF-κB/IL12信号通路可作为利什曼原虫感染治疗的靶点,CXCL10也有望成为潜在的治疗靶点;利什曼原虫感染后,出现类似病毒感染现象,推测抗病毒免疫疗法可能在对抗利什曼原虫感染中具有一定疗效。

Objective:To analyze changes of gene expression and signaling pathways of dendritic cells(DCs)in early stage of infection with Leishmania,to explore response of DCs after infection,and to search ideas for DEGs based immunotherapy after Leishmania infection.Methods:GEO database was used to download genechip data of DCs before and after infected with Leishmania,and differentially expressed genes(DEGs)were screened using RStudio software.Protein interaction network(PPI)was constructed for DEGs by STRING and core modules of differentially expressed proteins were screened by Cytoscape.DEGs were subjected to GO and KEGG enrichment analysis by RStudio software.Results:A total of 129 DEGs were selected,difference between IL12B and CXCL10 was most obvious,and 23 processes were enriched by GO analysis,which were mainly associated with cellular responses during viral infection andⅠ-IFN-related immune responses.Three signaling pathways were enriched by KEGG analysis,which were influenza A,measles,and DNA replication signaling pathways.Conclusion:Ⅰ-IFN signaling pathway and TLR4/NF-κB signaling pathway were activated upon on DCs infected with Leishmania,which could affect expression of IL12,and speculated thatⅠ-IFN/IL12 signaling pathway and TLR4/NF-κB/IL12 signaling pathway were expected to be targets for treatment of Leishmania infection.CXCL10 was also expected to be a potential therapeutic target.There was a phenomenon similar to viral infection after Leishmania infection,which conjectured that antiviral immunotherapy may be effective in treatment of Leishmania infection.