Modern Beijing sublineage of Mycobacterium tuberculosis shift macrophage into a hyperinflammatory status

The high prevalence of the modern Beijing sublineage of Mycobacterium tuberculosis 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 in vitro 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.

结核分枝杆菌（Mycobacterium tuberculosis）现代北京亚分支的高流行率可能与其毒力增强相关，但其背后的具体致病机制目前仍不甚明晰。我们此前已报道，现代北京菌株存在三酰甘油积累增强的现象。本研究发现，现代北京菌株在体外培养时生长速度更快，且可触发强烈的免疫应答与显著的巨噬细胞浸润。对感染现代北京亚分支菌株的骨髓源性巨噬细胞（bone marrow derived macrophages）进行转录组分析后发现，感染相关、胆固醇稳态及氨基酸代谢通路出现显著富集。通过RT–PCR（逆转录聚合酶链式反应）分析证实，促炎/杀菌细胞因子的表达出现上调，这一结果也与现代北京菌株感染的巨噬细胞内细菌载量降低的现象相一致。上述结果表明，现代北京菌株可诱导过度炎症应答，这或许意味着其具有更强的毒力，进而助力其在全球范围内的广泛流行。