The Legionnaires' disease bacterium (Legionella pneumophila) inhibits phagosome-lysosome fusion in human monocytes.
The Legionnaires' disease bacterium (Legionella pneumophila) inhibits phagosome-lysosome fusion in human monocytes.
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DOI：
10.1084/jem.158.6.2108
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发表时间：
1983-12-01
期刊：
影响因子：
--
通讯作者：
Horwitz MA
中科院分区：
文献类型：
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作者：
Horwitz MA
L.通过用二氧化钍（一种电子不透明的胶体标记物）预标记溶酶体和酸性磷酸酶细胞化学来研究嗜肺菌吞噬体和单核细胞溶酶体。含活L.在进入单核细胞后1h或进入单核细胞后4或8h，嗜肺菌不与次级溶酶体融合，此时核糖体衬里的L.嗜肺细胞复制泡形成。相反，大多数含福尔马林的吞噬体杀死了L。嗜肺菌、活肺炎链球菌和活大肠杆菌在进入单核细胞后1小时已与次级溶酶体融合。红霉素，一种有效的细菌蛋白质合成抑制剂，在完全抑制L。pneumophila细胞内增殖，对L.具有次级溶酶体的嗜肺菌吞噬体。然而，涂布活L. pneumophila与抗体或与抗体和补体部分克服了融合抑制。激活单核细胞也促进了一小部分含活L.具有次级溶酶体的嗜肺菌。酸性磷酸酶细胞化学显示，吞噬体含有活L。嗜肺细胞既不与初级溶酶体融合，也不与次级溶酶体融合。与含有活菌的吞噬体相反，大多数含有福尔马林杀死的L。酸性磷酸酶细胞化学染色显示嗜肺细胞与溶酶体融合。L的容量。嗜肺菌抑制吞噬体-溶酶体融合可能是细菌抵抗单核细胞杀微生物作用的关键机制。
The interactions between the L. pneumophila phagosome and monocyte lysosomes were investigated by prelabeling the lysosomes with thorium dioxide, an electron-opaque colloidal marker, and by acid phosphatase cytochemistry. Phagosomes containing live L. pneumophila did not fuse with secondary lysosomes at 1 h after entry into monocytes or at 4 or 8 h after entry by which time the ribosome-lined L. pneumophila replicative vacuole had formed. In contrast, the majority of phagosomes containing formalin-killed L. pneumophila, live Streptococcus pneumoniae, and live Escherichia coli had fused with secondary lysosomes by 1 h after entry into monocytes. Erythromycin, a potent inhibitor of bacterial protein synthesis, at a concentration that completely inhibits L. pneumophila intracellular multiplication, had no influence on fusion of L. pneumophila phagosomes with secondary lysosomes. However, coating live L. pneumophila with antibody or with antibody and complement partially overcame the inhibition of fusion. Also activating the monocytes promoted fusion of a small proportion of phagosomes containing live L. pneumophila with secondary lysosomes. Acid phosphatase cytochemistry revealed that phagosomes containing live L. pneumophila did not fuse with either primary or secondary lysosomes. In contrast to phagosomes containing live bacteria, the majority of phagosomes containing formalin-killed L. pneumophila were fused with lysosomes by acid phosphatase cytochemistry. The capacity of L. pneumophila to inhibit phagosome-lysosome fusion may be a critical mechanism by which the bacterium resists monocyte microbicidal effects.