The human macrophage mannose receptor directs Mycobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis.
The human macrophage mannose receptor directs Mycobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis.
复制标题
人类巨噬细胞甘露糖受体指导结核分枝杆菌脂肪氨基氨基甘氨酸介导的吞噬体生物发生。
DOI：
10.1084/jem.20051239
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发表时间：
2005-10-03
期刊：
影响因子：
--
通讯作者：
Schlesinger LS
中科院分区：
文献类型：
--
作者：
Kang PB;Azad AK;Torrelles JB;Kaufman TM;Beharka A;Tibesar E;DesJardin LE;Schlesinger LS
结核分枝杆菌（M.tb）在巨噬细胞中的存活部分是通过限制吞噬体-溶酶体（P-L）融合。结核分枝杆菌甘露糖加帽的脂阿拉伯甘露聚糖（ManLAM）阻断吞噬体成熟。模式识别甘露糖受体（MR）与ManLAM甘露糖帽结合，并介导人类巨噬细胞对杆菌的吞噬作用。使用定量电子显微镜和共聚焦显微镜，我们报告说，在吞噬过程中的MR ManLAM的参与是限制P-L融合的关键步骤。ManLAM微球的P-L融合在人巨噬细胞和MR表达细胞系中显著降低，但在缺乏受体的单核细胞中不显著降低。此外，MR阻断可逆转P-L融合抑制。通过Fcγ受体或树突状细胞特异性细胞内粘附分子3捕获非整合素或磷脂酰肌醇加帽的脂阿拉伯甘露聚糖进入，不会抑制P-L融合。ManLAM甘露糖帽结构在限制P-L融合中是必需的，并且需要完整的分子来维持这种表型。最后，在吞噬毒性结核分枝杆菌期间的MR阻断导致人巨噬细胞中P-L融合抑制的逆转（84.0 ± 5.1%对38.6 ± 0.6%）。因此，在吞噬过程中ManLAM与MR的结合将结核分枝杆菌引导至其初始吞噬体小生境，从而增强在人巨噬细胞中的存活。
Mycobacterium tuberculosis (M.tb) survives in macrophages in part by limiting phagosome–lysosome (P-L) fusion. M.tb mannose-capped lipoarabinomannan (ManLAM) blocks phagosome maturation. The pattern recognition mannose receptor (MR) binds to the ManLAM mannose caps and mediates phagocytosis of bacilli by human macrophages. Using quantitative electron and confocal microscopy, we report that engagement of the MR by ManLAM during the phagocytic process is a key step in limiting P-L fusion. P-L fusion of ManLAM microspheres was significantly reduced in human macrophages and an MR-expressing cell line but not in monocytes that lack the receptor. Moreover, reversal of P-L fusion inhibition occurred with MR blockade. Inhibition of P-L fusion did not occur with entry via Fcγ receptors or dendritic cell–specific intracellular adhesion molecule 3 grabbing nonintegrin, or with phosphatidylinositol-capped lipoarabinomannan. The ManLAM mannose cap structures were necessary in limiting P-L fusion, and the intact molecule was required to maintain this phenotype. Finally, MR blockade during phagocytosis of virulent M.tb led to a reversal of P-L fusion inhibition in human macrophages (84.0 ± 5.1% vs. 38.6 ± 0.6%). Thus, engagement of the MR by ManLAM during the phagocytic process directs M.tb to its initial phagosomal niche, thereby enhancing survival in human macrophages.
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影响因子：
56.9
作者：
Blander, JM;Medzhitov, R
通讯作者：
Medzhitov, R
影响因子：
15.3
作者：
Geijtenbeek, TBH;van Vliet, SJ;Koppel, EA;Sanchez-Hernandez, M;Vandenbroucke-Grauls, CMJE;Appelmelk, B;van Kooyk, Y
通讯作者：
van Kooyk, Y
影响因子：
4.8
作者：
Downey, GP;Botelho, RJ;Grinstein, S
通讯作者：
Grinstein, S
DOI：
10.1084/jem.172.6.1785
发表时间：
1990-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ezekowitz RA;Sastry K;Bailly P;Warner A
通讯作者：
Warner A
影响因子：
56.9
作者：
JOINER, KA;FUHRMAN, SA;MELLMAN, I
通讯作者：
MELLMAN, I