Plasmodium Falciparum Biology - Liver Stage

Liver Stage

After circulating in the bloodstream, the P. falciparum sporozoites enter hepatocytes. Before entering a hepatocyte the sporozoite typically engages in traversal of several cells. The reason for this behavior is not clear but it appears to reduce clearance of the sporozoites by Kupffer cells.

Once within a hepatocyte the parasite loses its apical complex and surface coat and transforms into a trophozoite. Within the parasitophorous vacuole of the hepatocyte, P. falciparum undergoes schizogonic development. In this stage, the nucleus divides multiple times with a concomitant increase in cell size but without cell segmentation. This exoerythrocytic schizogony stage of P. falciparum has a minimum duration of roughly 5.5 days. After segmentation, the parasite cells differentiate into merozoites.

Invasion of the hepatocytes appears to involve at least 2 proteins: sporozoite invasion-associated proteins (SIAP)-1 and -2. These proteins bind heparin sulfate and chondroitin sulfate type membrane receptors on host cells.

Productive invasion of the hepatocyte results in the creation of a digestive vacuole, while merely passing through to reach another hepatocyte does not. Invasion of the liver cell changes the properties of the cell itself. The cell membrane becomes rougher and the cell itself becomes significantly stiffer. The mechanism of these changes is currently unknown.

During this stage of development the sporozoite selectively discards organelles unnecessary for growth at this stage of the life cycle. Among these are the micronemes and the inner membrane complex.

The division of the liver stages into thousands of merozoites is a complex process. In parallel with nuclear division, the apicoplast and mitochondrion become two extensively branched and intertwining structures. The organelles subsequently undergo morphological and positional changes prior to cell division. Finally to form merozoites, the parasite undergoes cytokinesis.

After maturation, the merozoites are released from the hepatocytes and enter the erythrocytic portion of their life-cycle. Note that these cells do not reinfect hepatocytes.

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