Real-time visualization of Mycobacterium-macrophage interactions leading to initiation of granuloma formation in zebrafish embryos
Real-time visualization of Mycobacterium-macrophage interactions leading to initiation of granuloma formation in zebrafish embryos
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DOI：
10.1016/s1074-7613(02)00475-2
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发表时间：
2002-12-01
期刊：
影响因子：
32.4
通讯作者：
Ramakrishnan, L
中科院分区：
文献类型：
--
作者：
Davis, JM;Clay, H;Ramakrishnan, L
脊椎动物宿主感染致病性分枝杆菌（结核病的病原体），产生肉芽肿，高度组织化的结构，含有分化的巨噬细胞和淋巴细胞，隔离病原体。成年斑马鱼自然易患由海洋分枝杆菌引起的结核病。在这里，我们利用斑马鱼胚胎的光学透明度来成像M。海洋细菌感染。尽管胚胎还没有淋巴细胞，但感染导致形成具有肉芽肿病理标志的巨噬细胞聚集体，并激活先前鉴定的肉芽肿特异性分枝杆菌基因。因此，分枝杆菌-巨噬细胞相互作用可以仅在先天免疫的情况下启动肉芽肿形成。引人注目的是，感染可以改变正常胚胎巨噬细胞迁移的方向，甚至招募似乎致力于其发育决定的组织部位的巨噬细胞。
Infection of vertebrate hosts with pathogenic Mycobacteria, the agents of tuberculosis, produces granulomas, highly organized structures containing differentiated macrophages and lymphocytes, that sequester the pathogen. Adult zebrafish are naturally susceptible to tuberculosis caused by Mycobacterium marinum. Here, we exploit the optical transparency of zebrafish embryos to image the events of M. marinum infection in vivo. Despite the fact that the embryos do not yet have lymphocytes, infection leads to the formation of macrophage aggregates with pathological hallmarks of granulomas and activation of previously identified granuloma-specific Mycobacterium genes. Thus, Mycobacterium-macrophage interactions can initiate granuloma formation solely in the context of innate immunity. Strikingly, infection can redirect normal embryonic macrophage migration, even recruiting macrophages seemingly committed to their developmentally dictated tissue sites.