Cord factor trehalose 6,6′-dimycolate (TDM) mediates trafficking events during mycobacterial infection of murine macrophages
Cord factor trehalose 6,6′-dimycolate (TDM) mediates trafficking events during mycobacterial infection of murine macrophages
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DOI：
10.1099/mic.0.26226-0
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发表时间：
2003-08-01
期刊：
影响因子：
2.8
通讯作者：
Actor, JK
中科院分区：
文献类型：
--
作者：
Indrigo, J;Hunter, RL;Actor, JK
肺结核在肺肉芽肿性病变中的持久性是一个复杂的现象，细菌存活发生在免疫活性较高的局部区域。在一定程度上，生物体的存活可能与表面糖脂海藻糖(TDM)抑制宿主巨噬细胞内磷脂小泡之间的融合事件的能力有关。与此同时，TDM有助于巨噬细胞的激活，以及启动和维持肉芽肿反应所需的一系列事件。这可以增加对生物体的隔离，并进一步在宿主组织内存活和持续。对去除TDM的结核分枝杆菌的细菌活力、巨噬细胞因子和趋化因子反应以及细胞内转运进行了研究。表面脂的去除导致生物向酸性隔间的运输增加；用纯TDM或含有粗表面脂的石油醚提取物重建脱脂生物可恢复正常反应。使用TDM包裹的聚苯乙烯微珠表明，TDM可以调节细胞内的转运事件，以及影响巨噬细胞产生促炎分子。因此，TDM的存在可能是巨噬细胞内结核分枝杆菌成功感染和存活的重要决定因素。
The persistence of tuberculosis within pulmonary granulomatous lesions is a complex phenomenon, with bacterial survival occurring in a focal region of high immune activity. In part, the survival of the organism may be linked to the ability of the surface glycolipid trehalose 6,6'-dimycolate (TDM; cord factor) to inhibit fusion events between phospholipid vesicles inside the host macrophage. At the same time, TDM contributes to macrophage activation and a cascade of events required for initiation and maintenance of granulomatous responses. This allows increased sequestration of organisms and further survival and persistence within host tissues. Bacterial viability, macrophage cytokine and chemokine response, and intracellular trafficking were investigated in Mycobacterium tuberculosis from which TDM had been removed. Removal of surface lipids led to enhanced trafficking of organisms to acidic compartments; reconstitution of delipidated organisms with either pure TDM or the petroleum ether extract containing crude surface lipids restored normal responses. Use of TDM-coated polystyrene beads demonstrated that TDM can mediate intracellular trafficking events, as well as influence macrophage production of pro-inflammatory molecules. Thus, the presence of TDM may be an important determinant for successful infection and survival of M. tuberculosis within macrophages.