The Mycobacterium tuberculosis phagosome interacts with early endosomes and is accessible to exogenously administered transferrin
The Mycobacterium tuberculosis phagosome interacts with early endosomes and is accessible to exogenously administered transferrin
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DOI：
10.1084/jem.184.4.1349
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发表时间：
1996-10-01
影响因子：
15.3
通讯作者：
Horwitz, MA
中科院分区：
文献类型：
--
作者：
Clemens, DL;Horwitz, MA
先前的研究表明，人单核细胞来源的巨噬细胞中的结核分枝杆菌吞噬体获得早期和晚期内体的标记，但缺乏结核分枝杆菌吞噬体与内体室相互作用的直接证据。利用冷冻免疫金技术，我们发现结核分枝杆菌吞噬体以时间依赖性的方式获得外源添加的转铁蛋白。转铁蛋白的最大获取发生在15分钟内，获取动力学与结核分枝杆菌吞噬体与早期内体的相互作用一致。被感染的巨噬细胞在缺乏人转铁蛋白的培养基中孵育，将转铁蛋白赶出结核分枝杆菌吞噬体。另一方面，含有乳胶珠或热致死结核分枝杆菌的吞噬体不能获得转铁蛋白染色。这些和其他研究结果表明，结核分枝杆菌在吞噬体与早期和晚期内体相互作用的阶段阻止其吞噬体的成熟，但不与溶酶体相互作用。转铁蛋白内吞途径为抗菌药物靶向结核分枝杆菌吞噬体提供了一条新的途径。
Previous studies have demonstrated that the Mycobacterium tuberculosis phagosome in human monocyte-derived macrophages acquires markers of early and late endosomes, but direct evidence of interaction of the M. tuberculosis phagosome with the endosomal compartment has been lacking. Using the cryosection immunogold technique, we have found that the M. tuberculosis phagosome acquires exogenously added transferrin in a time-dependent fashion. Near-maximal acquisition of transferrin occurs within 15 min, kinetics of acquisition consistent with interaction of the M. tuberculosis phagosome with early endosomes. Transferrin is chased out of the M. tuberculosis phagosome by incubation of the infected macrophages in culture medium lacking human transferrin. Phagosomes containing latex beads or heat-killed M. tuberculosis, on the other hand, do not acquire staining for transferrin. These and other findings demonstrate that M. tuberculosis arrests the maturation of its phagosome at a stage at which the phagosome interacts with early and late endosomes, but not with lysosomes. The transferrin endocytic pathway potentially provides a novel route for targeting antimicrobials to the M. tuberculosis phagosome.