J Clin Invest. 2023 Mar 15;133(6):e168366. doi: 10.1172/JCI168366.
Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), infects primarily macrophages, causing them to differentiate into lipid-laden foamy macrophages that are a primary source of tissue destruction in patients with TB. In this issue of the JCI, Bedard et al. demonstrate that 1-tuberculosinyladenosine, a virulence factor produced by M. tuberculosis, caused lysosomal dysfunction associated with lipid storage in the phagolysosome of macrophages in a manner that mimicked lysosomal storage diseases. This work sheds light on how M. tuberculosis manipulates host lipid metabolism for its survival and opens avenues toward host-directed therapy against TB.
结核分枝杆菌是结核病(TB)的病原体,主要感染巨噬细胞,使其分化为富含脂质的泡沫巨噬细胞,这是结核病患者组织破坏的主要来源。在本期 JCI 中,Bedard 等人表明,结核分枝杆菌产生的毒力因子 1-结核分枝杆菌腺苷,以模拟溶酶体贮积病的方式导致溶酶体功能障碍,并伴有巨噬细胞吞噬溶酶体中的脂质贮积。这项工作揭示了结核分枝杆菌如何操纵宿主的脂质代谢以维持其生存,并为针对结核病的宿主导向治疗开辟了途径。