The effects of macrophage source on the mechanism of phagocytosis and intracellular survival of Leishmania
The effects of macrophage source on the mechanism of phagocytosis and intracellular survival of Leishmania
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DOI：
10.1016/j.micinf.2011.05.014
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发表时间：
2011-11-01
影响因子：
5.8
通讯作者：
Wilson, Mary E.
中科院分区：
文献类型：
--
作者：
Hsiao, Chia-Hung Christine;Ueno, Norikiyo;Wilson, Mary E.
利什曼原生动物是专性细胞内寄生物，在哺乳动物感染期间在巨噬细胞中复制。巨噬细胞的有效吞噬和存活是寄生虫毒力的重要决定因素。巨噬细胞系在维持细胞内查氏婴儿利什曼原虫（Lic）的能力方面存在显着差异。我们报告说，U937单核细胞系支持细胞内复制和细胞间传播的LIC在72小时后寄生虫添加，而原代人单核细胞衍生的巨噬细胞（MDM）没有。电子显微镜和活细胞成像表明，Lic前鞭毛体通过其前端锚定到MDM，并通过对称的伪足被吞噬。与此相反，U937细胞绑定LIC在不同的方向，并延长膜板重定向和内化寄生虫通过卷曲吞噬。在两种细胞类型中，Lic与寄生虫液泡（PV）膜紧密结合。在MDM吞噬后24小时，PV与表达LAMP-1的隔室融合，而U937细胞PV保持LAMP-1阴性。一种吞噬受体（CR 3）的表达在MDM中高于U937细胞，这使我们推测寄生虫的摄取通过这些细胞之间不同的途径进行。我们假设，吞噬机制与永生化的人巨噬细胞之间的不同，在随后的寄生虫细胞内的命运相应的差异。由Elsevier Masson SAS代表巴斯德研究所发布。
Leishmania spp. protozoa are obligate intracellular parasites that replicate in macrophages during mammalian infection. Efficient phagocytosis and survival in macrophages are important determinants of parasite virulence. Macrophage lines differ dramatically in their ability to sustain intracellular Leishmania infantum chagasi (Lic). We report that the U937 monocytic cell line supported the intracellular replication and cell-to-cell spread of Lic during 72 h after parasite addition, whereas primary human monocyte-derived macrophages (MDMs) did not. Electron microscopy and live cell imaging illustrated that Lic promastigotes anchored to MDMs via their anterior ends and were engulfed through symmetrical pseudopods. In contrast, U937 cells bound Lic in diverse orientations, and extended membrane lamellae to reorient and internalize parasites through coiling phagocytosis. Lic associated tightly with the parasitophorous vacuole (PV) membrane in both cell types. PVs fused with LAMP-1-expressing compartments 24 h after phagocytosis by MDMs, whereas U937 cell PVs remained LAMP-1 negative. The expression of one phagocytic receptor (CR3) was higher in MDMs than U937 cells, leading us to speculate that parasite uptake proceeds through dissimilar pathways between these cells. We hypothesize that the mechanism of phagocytosis differs between primary versus immortalized human macrophage cells, with corresponding differences in the subsequent intracellular fate of the parasite. Published by Elsevier Masson SAS on behalf of Institut Pasteur.