Manipulation of host hepatocytes by the malaria parasite for delivery into liver sinusoids

Science. 2006 Sep 1;313(5791):1287-90. doi: 10.1126/science.1129720. Epub 2006 Aug 3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Vessels / parasitology
  • Calcium / metabolism
  • Cell Adhesion
  • Cell Death
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cellular Structures / parasitology*
  • Cellular Structures / ultrastructure
  • Endothelial Cells / parasitology
  • Erythrocytes / parasitology
  • Hepatocytes / parasitology*
  • Hepatocytes / physiology
  • Hepatocytes / ultrastructure
  • Humans
  • Ionomycin / pharmacology
  • Liver / blood supply*
  • Liver / parasitology
  • Malaria / parasitology*
  • Mice
  • Mice, Inbred C57BL
  • Phagocytosis
  • Phosphatidylserines / metabolism
  • Plasmodium berghei / growth & development
  • Plasmodium berghei / pathogenicity*
  • Sporozoites / growth & development
  • Vacuoles / parasitology
  • Vacuoles / ultrastructure

Substances

  • Phosphatidylserines
  • Ionomycin
  • Calcium