Manipulation of host hepatocytes by the malaria parasite for delivery into liver sinusoids.
The merozoite stage of the malaria parasite that infects erythrocytes and causes the symptoms of the disease is initially formed inside host hepatocytes. However, the mechanism by which hepatic merozoites reach blood vessels (sinusoids) in the liver and escape the host immune system before invading erythrocytes remains unknown. Here, we show that parasites induce the death and the detachment of their host hepatocytes, followed by the budding of parasite-filled vesicles (merosomes) into the sinusoid lumen. Parasites simultaneously inhibit the exposure of phosphatidylserine on the outer leaflet of host plasma membranes, which act as "eat me" signals to phagocytes. Thus, the hepatocyte-derived merosomes appear to ensure both the migration of parasites into the bloodstream and their protection from host immunity.
Sturm
Angelika
A
Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany.
Amino
Rogerio
R
van de Sand
Claudia
C
Regen
Tommy
T
Retzlaff
Silke
S
Rennenberg
Annika
A
Krueger
Andreas
A
Pollok
Jörg-Matthias
JM
Menard
Robert
R
Heussler
Volker T
VT
D000818:Animals; D001808:Blood Vessels / Q000469:parasitology; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D016923:Cell Death; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D022082:Cellular Structures / Q000469:parasitology* / Q000648:ultrastructure; D042783:Endothelial Cells / Q000469:parasitology; D004912:Erythrocytes / Q000469:parasitology; D022781:Hepatocytes / Q000469:parasitology* / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D008099:Liver / Q000098:blood supply* / Q000469:parasitology; D008288:Malaria / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism; D010962:Plasmodium berghei / Q000254:growth & development / Q000472:pathogenicity*; D034101:Sporozoites / Q000254:growth & development; D014617:Vacuoles / Q000469:parasitology / Q000648:ultrastructure
D010718:Phosphatidylserines; D015759:Ionomycin; D002118:Calcium