Zhou Shuang, Zhang Ding, Li Dan, Wang Hankun, Ding Cairong, Song Jingrui, Huang Weifeng, Xia Xuan, Zhou Ziwei, Han Shanshan, Jin Zhu, Yan Bo, Gonzales Jacqueline, Via Laura E, Zhang Lu, Wang Decheng
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University; Institute of Infection and Inflammation, China Three Gorges University; College of Basic Medical Sciences, China Three Gorges University, Yichang 443002, P.R. China.
Department of Tuberculosis, The Third People's Hospital of Yichang, Yichang 443003, P.R. China.
iScience. 2024 Feb 12;27(3):109204. doi: 10.1016/j.isci.2024.109204. eCollection 2024 Mar 15.
Pathogenic mycobacteria orchestrate the complex cell populations known as granuloma that is the hallmark of tuberculosis. Foam cells, a lipid-rich cell-type, are considered critical for granuloma formation; however, the causative factor in foam cell formation remains unclear. Atherosclerosis is a chronic inflammatory disease characterized by the abundant accumulation of lipid-laden-macrophage-derived foam cells during which cholesterol 25-hydroxylase (CH25H) is crucial in foam cell formation. Here, we show that . (), a relative of . , induces foam cell formation, leading to granuloma development following CH25H upregulation. Moreover, the -driven increase in CH25H expression is associated with the presence of phthiocerol dimycocerosate, a determinant for virulence and integrity. CH25H- mice showed decreased foam cell formation and attenuated pathology. Atorvastatin, a recommended first-line lipid-lowering drug, promoted the elimination of and concomitantly reduced CH25H production. These results define a previously unknown role for CH25H in controlling macrophage-derived foam cell formation and Tuberculosis pathology.
致病性分枝杆菌构建了被称为肉芽肿的复杂细胞群体，而肉芽肿是结核病的标志。泡沫细胞是一种富含脂质的细胞类型，被认为对肉芽肿形成至关重要；然而，泡沫细胞形成的致病因素仍不清楚。动脉粥样硬化是一种慢性炎症性疾病，其特征是富含脂质的巨噬细胞衍生的泡沫细胞大量积聚，在此过程中胆固醇25-羟化酶（CH25H）在泡沫细胞形成中起关键作用。在这里，我们表明……（……的亲属）诱导泡沫细胞形成，导致CH25H上调后肉芽肿发展。此外，……驱动的CH25H表达增加与结核硬脂酸二霉菌酸酯的存在有关，结核硬脂酸二霉菌酸酯是……毒力和完整性的决定因素。CH25H基因敲除小鼠的泡沫细胞形成减少，病理变化减轻。阿托伐他汀是一种推荐的一线降脂药物，可促进……的清除并同时减少CH25H的产生。这些结果确定了CH25H在控制巨噬细胞衍生的泡沫细胞形成和结核病病理方面以前未知的作用。
