BACKGROUND 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). RESULTS 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. CONCLUSION 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.

中文翻译：

---

ABC转运蛋白和酰基转移酶1参与牛肺泡巨噬细胞中细胞内胆固醇介导的自噬反应，以应对卡介苗芽孢杆菌（BCG）感染。

背景技术了解致病机制对于开发新的结核病治疗是必不可少的，结核病是全世界重要的公共卫生负担。最近的研究表明，宿主胆固醇水平与宿主细胞中结核分枝杆菌（结核分枝杆菌，Mtb）感染的建立有关，其中细胞内胆固醇介导的ATP结合盒转运蛋白（ABC转运蛋白）和胆固醇酰基转移酶1（ACAT1）表现出调节由牛分枝杆菌卡尔梅特-瓜林（BCG）诱导的巨噬细胞自噬的能力。结果结果表明，响应于BCG感染，原代牛肺泡巨噬细胞（AMs）和鼠RAW264.7细胞中ABC-转运蛋白和ACAT1的表达下调。ABC转运蛋白和ACAT1的表达受抑制与细胞内游离胆固醇的降低有关，后者继而在分枝杆菌感染后诱导巨噬细胞自噬。这些结果强烈表明，ABC转运蛋白和ACAT1参与了细胞内胆固醇介导的AMs自噬，以响应BCG感染。结论因此，本研究为胆固醇代谢调节分枝杆菌感染后巨噬细胞自噬的调节机制提供了见解。