Essential role for cholesterol in entry of mycobacteria into macrophages
Essential role for cholesterol in entry of mycobacteria into macrophages
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DOI：
10.1126/science.288.5471.1647
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发表时间：
2000-06-02
期刊：
影响因子：
56.9
通讯作者：
Pieters, J
中科院分区：
文献类型：
--
作者：
Gatfield, J;Pieters, J
分枝杆菌是细胞内的病原体，可以入侵宿主巨噬细胞并在其中存活，从而在全球范围内造成重大健康问题。分枝杆菌侵入的分子机制尚不清楚。在此，我们报告胆固醇是巨噬细胞摄取分枝杆菌所必需的。胆固醇在分枝杆菌进入的部位积累，耗尽质膜胆固醇特别抑制分枝杆菌的摄取。胆固醇还介导了Taco的吞噬小体结合，Taco是一种外壳蛋白，可以防止溶酶体中分枝杆菌的降解。因此，通过进入宿主细胞的质膜富含胆固醇的区域，分枝杆菌可能确保它们随后在TACO包被的吞噬体内存活。
Mycobacteria are intracellular pathogens that can invade and survive within host macrophages, thereby creating a major health problem worldwide. The molecular mechanisms involved in mycobacterial entry are still poorly characterized. Here we report that cholesterol is essential for uptake of mycobacteria by macrophages. Cholesterol accumulated at the site of mycobacterial entry, and depleting plasma membrane cholesterol specifically inhibited mycobacterial uptake. Cholesterol also mediated the phagosomal association of TACO, a coat protein that prevents degradation of mycobacteria in lysosomes. Thus, by entering host cells at cholesterol-rich domains of the plasma membrane, mycobacteria may ensure their subsequent intracellular survival in TACO-coated phagosomes.