Transcriptional profiling of human macrophages during infection with Bordetella pertussis.

Bordetella pertussis, a strictly human reemerging 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 analyze the changes in gene expression profiles of human THP-1 macrophages resulting from B. pertussis infection. In parallel, we attempted to determine the changes in intracellular B. pertussis-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 programs. 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, in silico analyses identified large temporal changes in expression of specific gene subsets involved in signaling 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 B. pertussis cells switch from virulent to avirulent phase and actively adapt to intracellular environment, respectively.

百日咳博德特氏菌（Bordetella pertussis）是一种专性人类宿主的重现性病原体，亦是百日咳的致病菌，其借助多样毒力因子实现高效感染定植。本研究采用RNA测序（RNA sequencing）技术，分析百日咳博德特氏菌感染后人THP-1巨噬细胞的基因表达谱变化。与此同时，我们尝试解析与巨噬细胞相互作用后，细胞内百日咳博德特氏菌的特异性转录组谱变化。

分析结果显示，感染后6小时，THP-1巨噬细胞的全局基因表达谱发生广泛重编程。在高表达基因中，我们鉴定出编码细胞因子（cytokines）、趋化因子（chemokines）及转录调节因子（transcription regulators）的基因，这些因子参与诱导M1与M2型巨噬细胞极化程序（M1 and M2 macrophage polarization programs）。值得注意的是，若干参与凋亡（apoptosis）与炎症（inflammation）调控的宿主基因在感染后出现过表达——这类基因已知可被细胞内细菌病原体（intracellular bacterial pathogens）劫持调控。此外，计算机模拟分析（in silico analyses）发现，参与信号通路与代谢通路的特定基因子集的表达呈现显著的时序变化。

尽管细菌测序读段（sequencing reads）数量有限，我们仍观察到多数毒力因子的表达量下调，同时若干转录调节因子出现上调，这分别表明细胞内的百日咳博德特氏菌菌体从毒力相（virulent phase）转变为非毒力相（avirulent phase），并主动适应细胞内环境。