Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, Yinchuan, China.
College of Life Science, Ningxia University, Yinchuan, 750021, Ningxia, China.
BMC Immunol. 2020 May 12;21(1):26. doi: 10.1186/s12865-020-00356-x.
Understanding pathogenic mechanisms is imperative for developing novel treatment to the tuberculosis, an important public health burden worldwide. Recent studies demonstrated that host cholesterol levels have implications in the establishment of Mycobacterium tuberculosis (M. tuberculosis, Mtb) infection in host cells, in which the intracellular cholesterol-mediated ATP-binding cassette transporters (ABC-transporters) and cholesterol acyltransferase1 (ACAT1) exhibited abilities to regulate macrophage autophagy induced by Mycobacterium bovis bacillus Calmette-Guérin (BCG).
The results showed that a down-regulated expression of the ABC-transporters and ACAT1 in primary bovine alveolar macrophages (AMs) and murine RAW264.7 cells in response to a BCG infection. The inhibited expression of ABC-transporters and ACAT1 was associated with the reduction of intracellular free cholesterol, which in turn induced autophagy in macrophages upon to the Mycobacterial infection. These results strongly suggest an involvement of ABC-transporters and ACAT1 in intracellular cholesterol-mediated autophagy in AMs in response to BCG infection.
This study thus provides an insight into into a mechanism by which the cholesterol metabolism regulated the autophagy in macrophages in response to mycobacterial infections.
了解致病机制对于开发治疗结核病的新方法至关重要，结核病是全球重要的公共卫生负担。最近的研究表明，宿主胆固醇水平对结核分枝杆菌（Mycobacterium tuberculosis，Mtb）在宿主细胞中感染的建立有影响，其中细胞内胆固醇介导的 ABC 转运体（ABC-transporters）和胆固醇酰基转移酶 1（ACAT1）能够调节牛分枝杆菌卡介苗（BCG）诱导的巨噬细胞自噬。
结果表明，原发性牛肺泡巨噬细胞（AMs）和鼠 RAW264.7 细胞对 BCG 感染的 ABC 转运体和 ACAT1 的表达下调。ABC 转运体和 ACAT1 的表达抑制与细胞内游离胆固醇减少有关，这反过来又在分枝杆菌感染时诱导巨噬细胞自噬。这些结果强烈表明 ABC 转运体和 ACAT1 参与了 AMs 对 BCG 感染的细胞内胆固醇介导的自噬。
因此，本研究深入了解了胆固醇代谢在分枝杆菌感染时调节巨噬细胞自噬的机制。
