Differences in human macrophage receptor usage, lysosomal fusion kinetics and survival between logarithmic and metacyclic Leishmania infantum chagasi promastigotes.

Differences in human macrophage receptor usage, lysosomal fusion kinetics and survival between logarithmic and metacyclic Leishmania infantum chagasi promastigotes.
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DOI:
10.1111/j.1462-5822.2009.01374.x
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发表时间:
2009-12
影响因子:
3.4
通讯作者:
Wilson ME
Wilson ME
中科院分区:
生物学2区
文献类型:
--
作者:
Ueno N;Bratt CL;Rodriguez NE;Wilson ME

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专性细胞内原虫婴儿利什曼原虫(Lic)通过巨噬细胞进行受体介导的吞噬作用,随后吞噬酶体成熟一过性延迟。我们发现,人单核细胞来源的巨噬细胞(MDM)吞噬毒力Lic超环前鞭毛体或无毒对数前鞭毛体的途径不同。对数和亚环前鞭毛体都是通过第三补体受体(CR3)排列的隔室进入MDM的。相反,许多对数前鞭毛虫通过甘露糖受体(MR)排列的空泡进入,而大多数超环前鞭毛虫则没有(p<0.005)。CR3阳性的囊泡内含有小窝蛋白-1蛋白,提示CR3在吞噬过程中定位于小窝。进入后,吞噬酶体成熟和细胞内存活的动力学也不同。含有超环寄生虫的空泡在吞噬后的早期不积累溶酶体相关膜蛋白-1(LAMP-1),而含有对数前鞭毛体的空泡则有。MDMS吞噬的对数细胞数多于亚环型前鞭毛体,但亚环型最终以更高的效率在细胞内复制。这些数据表明,毒力超环型利什曼原虫前鞭毛虫不能连接巨噬细胞MR,并通过最终提高细胞内存活率的途径进入。毒力较强的利什曼原虫相对静止的进入。进入巨噬细胞可能是由于超环前鞭毛体选择性地绕过有害的进入途径的能力。
The obligate intracellular protozoan, Leishmania infantum chagasi (Lic) undergoes receptor-mediated phagocytosis by macrophages, followed by a transient delay in phagolysosome maturation. We found differences in the pathway through which virulent Lic metacyclic promastigotes or avirulent logarithmic promastigotes are phagocytosed by human monocyte-derived macrophages (MDMs). Both logarithmic and metacyclic promastigotes entered MDMs through a compartment lined by the third complement receptor (CR3). In contrast, many logarithmic promastigotes entered through vacuoles lined by mannose receptors (MR) whereas most metacyclic promastigotes did not (p < 0.005). CR3 positive vacuoles containing metacyclic promastigotes stained for caveolin-1 protein, suggesting CR3 localizes in caveolae during phagocytosis. Following entry, the kinetics of phagolysosomal maturation and intracellular survival also differed. Vacuoles containing metacyclic parasites did not accumulate lysosome-associated membrane protein-1 (LAMP-1) at early times after phagocytosis, whereas vacuoles with logarithmic promastigotes did. MDMs phagocytosed greater numbers of logarithmic than metacyclic promastigotes, yet metacyclics ultimately replicated intracellularly with greater efficiency. These data suggest that virulent metacyclic Leishmania promastigotes fail to ligate macrophage MR, and enter through a path that ultimately enhances intracellular survival. The relatively quiescent entry of virulent Leishmania spp. into macrophages may be accounted for by the ability of metacyclic promastigotes to selectively bypass deleterious entry pathways.
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