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: 8.06). 09/2011; 7(9):e1002224. DOI: 10.1371/journal.ppat.1002224
Source: PubMed

ABSTRACT 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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Available from: Christine Lehmann, Aug 25, 2015
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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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    Cellular Microbiology 03/2014; 16(5). DOI:10.1111/cmi.12288 · 4.82 Impact Factor
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    • "Hypoxia-treated hepatocytes exhibited a similar increase in susceptibility to P. yoelii infection (Fig. 2B,D,F; supplementary material Fig. S1B), suggesting that the observed effect of hypoxia is not restricted to a particular Plasmodium spp. Because P. berghei liver-stage infections mature at 55-65 hours post-infection in vitro (Graewe et al., 2011), P. berghei EEF sizes were quantified at 56 hours and 65 hours post-infection to address the possibility that hypoxia could be speeding up parasite development instead of increasing the potential for parasite growth. P. berghei EEFs were larger in hypoxic cultures at 48, 56 and 65 hours post-infection (supplementary material Fig. S1F). "
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    Disease Models and Mechanisms 11/2013; 7(2). DOI:10.1242/dmm.013490 · 5.54 Impact Factor
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    • "Further work is required to understand how the parasite triggers the induction of this enzyme. Finally, in vitro and in vivo studies have shown that developing parasites evade the attack of immune cells by inhibiting host cell apoptosis (Leiriao et al., 2005; van de Sand et al., 2005) and by generating merozoites that are covered by the host cell membrane (Sturm et al., 2006; Graewe et al., 2011). Interestingly, merozoite-filled merosomes budding off from infected hepatocytes inhibit the exposure of phosphatidylserine, a phagocyte ligand, on their membrane. "
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