Organelle membrane proteomics reveals differential influence of mycobacterial lipoglycans on macrophage phagosome maturation and autophagosome accumulation.
Organelle membrane proteomics reveals differential influence of mycobacterial lipoglycans on macrophage phagosome maturation and autophagosome accumulation.
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DOI：
10.1021/pr100688h
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发表时间：
2011-01-07
影响因子：
4.4
通讯作者：
Bertozzi, Carolyn R.
中科院分区：
文献类型：
--
作者：
Shui, Wenqing;Petzold, Christopher J.;Redding, Alyssa;Liu, Jun;Pitcher, Austin;Sheu, Leslie;Hsieh, Tsung-yen;Keasling, Jay D.;Bertozzi, Carolyn R.
分枝杆菌细胞壁组分脂阿拉伯甘露聚糖（LAM）已被描述为结核分枝杆菌的关键毒力因子之一。在M中用甘露糖帽修饰该脂聚糖的末端阿拉伯聚糖残基。结核分枝杆菌或耻垢分枝杆菌中的磷酸肌醇帽导致不同的宿主免疫应答。鉴于M。结核分枝杆菌通常在被巨噬细胞吞噬后持续存在于吞噬体空泡中，我们在用从两种分枝杆菌物种纯化的LAM处理巨噬细胞后对该细胞器进行了蛋白质组学分析。吞噬体蛋白质的定量变化表明甘露糖加帽的LAM在调节蛋白质运输途径中具有独特的作用，这些蛋白质运输途径有助于阻止吞噬体成熟。受我们的蛋白质组学数据的启发，我们进行了进一步的实验，表明只有来自M。结核抑制自噬空泡在巨噬细胞中的积累，提示这种毒力相关脂质的新功能。LAM被认为是结核分枝杆菌的关键毒力因子之一。在M中用甘露糖帽修饰该脂聚糖的末端阿拉伯聚糖残基。结核分枝杆菌或耻垢分枝杆菌中的磷酸肌醇帽导致不同的宿主免疫应答。鉴于M。结核分枝杆菌通常在被巨噬细胞吞噬后持续存在于吞噬体空泡中，我们在用从两种分枝杆菌物种纯化的LAM处理巨噬细胞后对该细胞器进行了蛋白质组学分析。
The mycobacterial cell wall component lipoarabinomannan (LAM) has been described as one of the key virulence factors of Mycobacterium tuberculosis. Modification of the terminal arabinan residues of this lipoglycan with mannose caps in M. tuberculosis or with phosphoinositol caps in Mycobacterium smegmatis results in distinct host immune responses. Given that M. tuberculosis typically persists in the phagosomal vacuole after being phagocytosed by macrophages, we performed a proteomic analysis of that organelle after treatment of macrophages with LAMs purified from the two mycobacterial species. The quantitative changes in phagosomal proteins suggested a distinct role for mannose-capped LAM in modulating protein trafficking pathways that contribute to the arrest of phagosome maturation. Enlightened by our proteomic data, we performed further experiments to show that only the LAM from M. tuberculosis inhibits accumulation of autophagic vacuoles in the macrophage, suggesting a new function for this virulence-associated lipid. LAM has been described as one of the key virulence factors of Mycobacterium tuberculosis. Modification of the terminal arabinan residues of this lipoglycan with mannose caps in M. tuberculosis or with phosphoinositol caps in Mycobacterium smegmatis results in distinct host immune responses. Given that M. tuberculosis typically persists in the phagosomal vacuole after being phagocytosed by macrophages, we performed a proteomic analysis of that organelle after treatment of macrophages with LAMs purified from the two mycobacterial species.
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影响因子：
4.5
作者：
Beatty, WL;Rhoades, ER;Russell, DG
通讯作者：
Russell, DG
影响因子：
21.3
作者：
Kanai, F;Liu, H;Yaffe, MB
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Yaffe, MB
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15.3
作者：
Clemens, DL;Horwitz, MA
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Horwitz, MA
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Davanger, S;Bock, JB;Scheller, RH
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Scheller, RH
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