Host but not parasite cholesterol controls Toxoplasma cell entry by modulating organelle discharge

被引:105
作者
Coppens, I [1 ]
Joiner, KA [1 ]
机构
[1] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA
关键词
D O I
10.1091/mbc.E02-12-0830
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Host cell cholesterol is implicated in the entry and replication of an increasing number of intracellular microbial pathogens. Although uptake of viral particles via cholesterol-enriched caveolae is increasingly well described, the requirement of cholesterol for internalization of eukaryotic pathogens is poorly understood and is likely to be partly organism specific. We examined the role of cholesterol in active host cell invasion by the protozoan parasite Toxoplasma gondii. The parasitophorous vacuole membrane (PVM) surrounding T. gondii contains cholesterol at the time of invasion. Although cholesterol-enriched parasite apical organelles termed rhoptries discharge at the time of cell entry and contribute to PVM formation, surprisingly, rhoptry cholesterol is not necessary for this process. In contrast, host plasma membrane cholesterol is incorporated into the forming PVM during invasion, through a caveolae-independent mechanism. Unexpectedly, depleting host cell plasma membrane cholesterol blocks parasite internalization by reducing the release of rhoptry proteins that are necessary for invasion. Cholesterol back-addition into host plasma membrane reverses this inhibitory effect of depletion on parasite secretion. These data define a new mechanism by which host cholesterol specifically controls entry of an intracellular pathogen.
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收藏
页码:3804 / 3820
页数:17
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