Petráčková Denisa, Farman Mariam R, Amman Fabian, Linhartová Irena, Dienstbier Ana, Kumar Dilip, Držmíšek Jakub, Hofacker Ivo, Rodriguez Maria Eugenia, Večerek Branislav
Institute of Microbiology of the Czech Academy of Sciences, Laboratory of Post-transcriptional Control of Gene Expression, Prague, Czech Republic.
Institute for Theoretical Chemistry, University of Vienna, Vienna, Austria.
RNA Biol. 2020 May;17(5):731-742. doi: 10.1080/15476286.2020.1727694. Epub 2020 Feb 19.
, a strictly human re-emerging pathogen and the causative agent of whooping cough, exploits a broad variety of virulence factors to establish efficient infection. Here, we used RNA sequencing to analyse the changes in gene expression profiles of human THP-1 macrophages resulting from infection. In parallel, we attempted to determine the changes in intracellular -specific transcriptomic profiles resulting from interaction with macrophages. Our analysis revealed that global gene expression profiles in THP-1 macrophages are extensively rewired 6 h post-infection. Among the highly expressed genes, we identified those encoding cytokines, chemokines, and transcription regulators involved in the induction of the M1 and M2 macrophage polarization programmes. Notably, several host genes involved in the control of apoptosis and inflammation which are known to be hijacked by intracellular bacterial pathogens were overexpressed upon infection. Furthermore, analyses identified large temporal changes in expression of specific gene subsets involved in signalling and metabolic pathways. Despite limited numbers of the bacterial reads, we observed reduced expression of majority of virulence factors and upregulation of several transcriptional regulators during infection suggesting that intracellular cells switch from virulent to avirulent phase and actively adapt to intracellular environment, respectively.
百日咳杆菌是一种严格意义上的人类再度出现的病原体,也是百日咳的致病因子,它利用多种毒力因子来建立有效的感染。在此,我们使用RNA测序来分析百日咳杆菌感染导致的人类THP-1巨噬细胞基因表达谱的变化。同时,我们试图确定与巨噬细胞相互作用导致的细胞内百日咳杆菌特异性转录组谱的变化。我们的分析表明,感染后6小时,THP-1巨噬细胞中的全局基因表达谱被广泛重排。在高表达基因中,我们鉴定出了那些编码参与M1和M2巨噬细胞极化程序诱导的细胞因子、趋化因子和转录调节因子的基因。值得注意的是,一些已知被细胞内细菌病原体劫持的参与细胞凋亡和炎症控制的宿主基因在感染后过度表达。此外,分析确定了参与信号传导和代谢途径的特定基因子集的表达存在较大的时间变化。尽管细菌读数数量有限,但我们观察到感染期间大多数毒力因子的表达降低,以及几种转录调节因子的上调,这分别表明细胞内百日咳杆菌从有毒阶段转变为无毒阶段,并积极适应细胞内环境。