Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College and Shanghai Public Health Clinical Center, Fudan University, Shanghai, People's Republic of China.
The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences/University of Chinese Academy of Sciences, Shanghai, People's Republic of China.
Emerg Microbes Infect. 2022 Dec;11(1):715-724. doi: 10.1080/22221751.2022.2037395.
The high prevalence of the modern Beijing sublineage of may be related to increased virulence, although the responsible mechanisms remain poorly understood. We previously described enhanced triacylglycerol accumulation in modern Beijing strains. Here we show that modern Beijing strains grow faster and trigger a vigorous immune response and pronounced macrophage infiltration. Transcriptomic analysis of bone marrow derived macrophages infected with modern Beijing lineage strains revealed a significant enrichment of infection, cholesterol homeostasis and amino acid metabolic pathways. The upregulation of proinflammatory / bactericidal cytokines was confirmed by RT-PCR analysis, which is also in consistent with the reduced bacterial burden in modern strains infected macrophages. These results suggest that modern Beijing strains elicit a hyperinflammatory response which might indicate a stronger virulence and contribute to their extensive global prevalence.
可能与毒力增强有关,尽管其相关机制仍不清楚。我们之前描述了现代北京谱系菌株中三酰甘油积累增加。这里我们显示现代北京谱系菌株生长更快,引发强烈的免疫反应和明显的巨噬细胞浸润。用现代北京谱系菌株感染骨髓来源的巨噬细胞的转录组分析显示感染、胆固醇稳态和氨基酸代谢途径显著富集。通过 RT-PCR 分析证实了促炎/杀菌细胞因子的上调,这也与感染巨噬细胞的现代菌株中细菌负荷减少一致。这些结果表明,现代北京谱系菌株引发了过度的炎症反应,这可能表明更强的毒力,并有助于它们在全球的广泛流行。