Dynamic life and death interactions between Mycobacterium smegmatis and J774 macrophages
Dynamic life and death interactions between Mycobacterium smegmatis and J774 macrophages
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DOI：
10.1111/j.1462-5822.2005.00675.x
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发表时间：
2006-06-01
影响因子：
3.4
通讯作者：
Griffiths, G
中科院分区：
文献类型：
--
作者：
Anes, E;Peyron, P;Griffiths, G
内化到巨噬细胞后，非致病性分支杆菌在吞噬体内被杀死。致病性分枝杆菌可以阻止吞噬体成熟并在吞噬体内生长，但在某些条件下也可以被巨噬细胞杀死。杀伤机制知之甚少，虽然吞噬溶酶体融合和一氧化氮（NO）的生产牵连。我们启动了一项系统性分析，探讨巨噬细胞如何杀死“非致病性”耻垢分枝杆菌。该系统是动态的，包括初始杀灭期，然后是细菌增殖，随后是两个额外的杀灭阶段。NO的合成代表了最早的杀伤因子，但其合成在第一个杀伤期停止。吞噬体肌动蛋白的组装和融合与晚期内吞细胞器相一致的第一和最后的杀伤阶段，而吞噬体内容物和膜的回收与细菌的生长相一致。吞噬体酸化和获得的液泡（V）ATP酶遵循不同的模式与后来的杀伤阶段相一致。此外，V-ATP酶定位于囊泡不同于经典的晚期内体和溶酶体。MAP激酶p38是所有研究过程的关键调节剂，除了NO合成，其促进宿主的某些功能，同时被活细菌篡夺其他功能。数学模型认为，周期性的高和低细胞杀伤活性比连续过程更有效。
After internalization into macrophages non-pathogenic mycobacteria are killed within phagosomes. Pathogenic mycobacteria can block phagosome maturation and grow inside phagosomes but under some conditions can also be killed by macrophages. Killing mechanisms are poorly understood, although phago-lysosome fusion and nitric oxide (NO) production are implicated. We initiated a systematic analysis addressing how macrophages kill 'non-pathogenic'Mycobacterium smegmatis. This system was dynamic, involving periods of initial killing, then bacterial multiplication, followed by two additional killing stages. NO synthesis represented the earliest killing factor but its synthesis stopped during the first killing period. Phagosome actin assembly and fusion with late endocytic organelles coincided with the first and last killing phase, while recycling of phagosome content and membrane coincided with bacterial growth. Phagosome acidification and acquisition of the vacuolar (V) ATPase followed a different pattern coincident with later killing phases. Moreover, V-ATPase localized to vesicles distinct from classical late endosomes and lysosomes. Map kinase p38 is a crucial regulator of all processes investigated, except NO synthesis, that facilitated the host for some functions while being usurped by live bacteria for others. A mathematical model argues that periodic high and low cellular killing activity is more effective than is a continuous process.