Kinetics of the intracellular differentiation of Leishmania amazonensis and internalization of host MHC molecules by the intermediate parasite stages
Kinetics of the intracellular differentiation of Leishmania amazonensis and internalization of host MHC molecules by the intermediate parasite stages
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DOI：
10.1017/s0031182001007387
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发表时间：
2001-03-01
期刊：
影响因子：
2.4
通讯作者：
Antoine, JC
中科院分区：
文献类型：
--
作者：
Courret, N;Frehel, C;Antoine, JC
利什曼原虫在哺乳动物中的建立依赖于巨噬细胞内元环原毛毛体向无尾毛毛体的转化。研究了这一过程的动力学，用小鼠巨噬细胞感染了亚马逊河蛭的超环原乳螺菌。在5天的时间里，无尾线虫的特征出现，包括大溶酶体样细胞器，称为大体，阶段特异性抗原，高半胱氨酸蛋白酶活性和对l -亮氨酸甲酯的敏感性。大体在48小时被观察到，但这些细胞器的可能前体在12小时被检测到。在吞噬后的5到12小时，检测到的promastigote特异性分子被下调，而所研究的amastigote特异性抗原在2到12-24小时被检测到。半胱氨酸蛋白酶活性和对l -亮氨酸甲酯的敏感性在24小时被检测到。数据表明，在48小时，寄生虫表现出一些无尾体特征，但完全分化至少需要5天。大体或大体前体的出现以及半胱氨酸蛋白酶活性的上升与寄生虫内化并很可能降解宿主MHC分子的能力密切相关。寄生虫对宿主细胞分子的内化发生在分化过程的早期，这一事实证明了这一机制在寄生虫生存中的作用。
The establishment of Leishmania in mammals depends on the transformation of metacyclic promastigotes into amastigotes within macrophages. The kinetics of this process was examined using mouse macrophages infected with metacyclic promastigotes of L. amazonensis. The appearance of amastigote characteristics, including large lysosome-like organelles called megasomes, stage-specific antigens, high cysteine protease activity and sensitivity to L-leucine methyl ester, was followed over a 5-day period. Megasomes were observed at 48 h but probable precursors of these organelles were detected at 12 h p.i. The promastigote-specific molecules examined were down-regulated within 5 to 12h after phagocytosis whereas the amastigote-specific antigens studied were detectable from 2 to 12-24 h. An increase in the cysteine protease activity and in sensitivity to L-leucine methyl ester of the parasites was detected from 24 h. The data indicate that at 48 h p.i., parasites exhibit several amastigote features but that complete differentiation requires at least 5 days. The appearance of megasomes or of megasome precursors and the rise in cysteine protease activity correlate quite well with the capacity of parasites to internalize and very likely degrade host MHC molecules. The fact that internalization by the parasites of host cell molecules occurs very early during the differentiation process argues for a role of this mechanism ill parasite survival.