The Host Endocytic Pathway is Essential for Plasmodium berghei Late Liver Stage Development

• Published in: Traffic (Copenhagen, Denmark) Denmark), 2012-10, Vol.13 (10), p.1351-1363
• Main Authors: Lopes da Silva, Mafalda, Thieleke‐Matos, Carolina, Cabrita‐Santos, Laura, Ramalho, José S., Wavre‐Shapton, Silène T., Futter, Clare E., Barral, Duarte C., Seabra, Miguel C.
• Format: Article
• Language: English
• Subjects: Animals; Cytoplasmic Vesicles - chemistry; endocytic pathway; Endocytosis; Female; Hepatocytes - metabolism; Hepatocytes - parasitology; Host-Parasite Interactions; late endosome; Liver; liver stage infection; Lysosomal Membrane Proteins - analysis; lysosome; Malaria; Mice; Mice, Inbred C57BL; Parasites; Plasmodium berghei; Plasmodium berghei - growth & development; Plasmodium berghei - metabolism; rab GTP-Binding Proteins - analysis; rab7 GTP-Binding Proteins; Schizonts - growth & development; Tetraspanin 30 - analysis; Tumor Cells, Cultured
• ISSN: 1398-9219; 1600-0854
• DOI: 10.1111/j.1600-0854.2012.01398.x

The obligate intracellular liver stage of the Plasmodium parasite represents a bottleneck in the parasite life cycle and remains a promising target for therapeutic intervention. During this stage, parasites undergo dramatic morphological changes and achieve one of the fastest replication rates among eukaryotic species. Nevertheless, relatively little is known about the parasite interactions with the host hepatocyte. Using immunofluorescence, live cell imaging and electron microscopy, we show that Plasmodium berghei parasites are surrounded by vesicles from the host late endocytic pathway. We found that these vesicles are acidic and contain the membrane markers Rab7a, CD63 and LAMP1. When host cell vesicle acidification was disrupted using ammonium chloride or Concanamycin A during the late liver stage of infection, parasite survival was not affected, but schizont size was significantly decreased. Furthermore, when the host cell endocytic pathway was loaded with BSA‐gold, gold particles were found within the parasite cytoplasm, showing the transport of material from the host endocytic pathway toward the parasite interior. These observations reveal a novel Plasmodium–host interaction and suggest that vesicles from the host endolysosomal pathway could represent an important source of nutrients exploited by the fast‐growing late liver stage parasites.