The host endocytic pathway is essential for Plasmodium berghei late liver stage development.
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.
CEDOC, Faculdade de Ciências Médicas, FCM, Universidade Nova de Lisboa, Lisboa, 1169-056, Portugal; Instituto Gulbenkian de Ciência, Oeiras, 2780-156, Portugal.
Mafalda
M
Lopes da Silva
Carolina
C
Thieleke-Matos
Laura
L
Cabrita-Santos
José S
JS
Ramalho
Silène T
ST
Wavre-Shapton
Clare E
CE
Futter
Duarte C
DC
Barral
Miguel C
MC
Seabra
D000818:Animals; D022162:Cytoplasmic Vesicles / Q000737:chemistry; D004705:Endocytosis; D005260:Female; D022781:Hepatocytes / Q000378:metabolism* / Q000469:parasitology*; D006790:Host-Parasite Interactions; D051907:Lysosomal Membrane Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000254:growth & development* / Q000378:metabolism*; D052939:Schizonts / Q000254:growth & development; D060149:Tetraspanin 30 / Q000032:analysis; D014407:Tumor Cells, Cultured; D020691:rab GTP-Binding Proteins / Q000032:analysis; D000090802:rab7 GTP-Binding Proteins; D052118:Lysosomal-Associated Membrane Protein 1
D051907:Lysosomal Membrane Proteins; D060149:Tetraspanin 30; D020691:rab GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins; C554587:Cd63 protein, mouse; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1