Hostile Takeover by Plasmodium: Reorganization of Parasite and Host Cell Membranes during Liver Stage Egress

Malaria Lab I, Department of Molecular Parasitology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
PLoS Pathogens (Impact Factor: 7.56). 09/2011; 7(9):e1002224. DOI: 10.1371/journal.ppat.1002224
Source: PubMed


The protozoan parasite Plasmodium is transmitted by female Anopheles mosquitoes and undergoes obligatory development within a parasitophorous vacuole in hepatocytes before it is released into the bloodstream. The transition to the blood stage was previously shown to involve the packaging of exoerythrocytic merozoites into membrane-surrounded vesicles, called merosomes, which are delivered directly into liver sinusoids. However, it was unclear whether the membrane of these merosomes was derived from the parasite membrane, the parasitophorous vacuole membrane or the host cell membrane. This knowledge is required to determine how phagocytes will be directed against merosomes. Here, we fluorescently label the candidate membranes and use live cell imaging to show that the merosome membrane derives from the host cell membrane. We also demonstrate that proteins in the host cell membrane are lost during merozoite liberation from the parasitophorous vacuole. Immediately after the breakdown of the parasitophorous vacuole membrane, the host cell mitochondria begin to degenerate and protein biosynthesis arrests. The intact host cell plasma membrane surrounding merosomes allows Plasmodium to mask itself from the host immune system and bypass the numerous Kupffer cells on its way into the bloodstream. This represents an effective strategy for evading host defenses before establishing a blood stage infection.

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    • "To access the bloodstream, liver-stage merozoites must leave hepatocytes and cross both the Disse and sinusoid spaces, where they are vulnerable to be attacked by phagocytes including KCs and DCs. To avoid host cell defense mechanisms, merozoites bud from detached hepatocytes in merosomes [4, 47], which are covered with host cell-derived membranes [48]. During this process, the infected hepatocyte dies, but merozoites uptake Ca2+ and maintain low Ca2+ levels in the host cell to block the exposure of PS (phosphatidylserine) on the outer leaflet of the dying cells [4, 47]. "
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    • "Several recent publications provided increasing evidence for an inside-out egress of the malaria parasite from the erythrocyte, during which the breakdown of the PVM precedes rupture of the EM (Glushakova et al., 2010; Chandramohanadas et al., 2011; Graewe et al., 2011; Sologub et al., 2011; reviewed in Wirth and Pradel, 2012). However, the molecular mechanisms of the inside-out egress are not fully known yet. "
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