Malaria parasites can bud from hepatocytes.

HEUSSLER/AAAS

Malaria parasites half kill their liver cell hosts, and then hide out in the shattered remnants, say Angelika Sturm, Volker Heussler (Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany), and colleagues. The disguise allows them to escape from the macrophage-rich liver into the general bloodstream; once there they can invade red blood cells.

This complex bit of subterfuge contrasts with the simple grow-and-burst mechanism that the parasite uses to eventually escape from red blood cells. “People extrapolated from the red blood cell situtation,” says Heussler. “But if hepatocytes would burst, [the parasites] would have to individually find their way through the endothelium to the blood vessels and even then they would not be safe—the [liver's] vessels are packed with macrophages.”

A simple burst was, however, what Heussler first hoped to see in vitro. Instead he saw the infected liver cells detach and float in the medium. These cells were half dead—their nuclei and mitochondria were damaged—but they did not look dead to macrophages observing from outside. The parasites accumulated calcium, and therefore the cell's scramblase enzyme did not flip phosphatidylserine (PS) to face the outside of the cell. Without the tell-tale PS facing outwards, macrophages cannot identify the cell as a target that is dead and should be eaten.

Parasites were also present in membrane-bound vesicles that did not contain nuclei. In vivo, these vesicles (dubbed merosomes) could be seen slowly oozing out of liver cells, with parasites apparently being shuffled into them before the merosomes departed. The merosomes often squeezed through endothelial walls into blood vessels, with macrophage proteases perhaps creating a path for the exit.

The force for merosome movement might be supplied by the uninfected cells, which try to knit together while expelling the dying cells. Merosomes then appear to bide their time until they have escaped the liver, before releasing parasites in a spaced series of volcanic bursts.

Reference:

Sturm, A., et al.
2006
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Science.
doi:.