Malaria sporozoite rite of passage.

Abstract

Parasitology textbooks would have you believe that after being delivered via a mosquito bite into the peripheral circulation, a Plasmodium sporozoite homes rapidly to the liver to infect a single hepatocyte. Sporozoites are transported by the blood to the liver microcirculation where they come into contact with the sinusoidal cell layer composed of endothelial and Kupffer cells, the stationary phagocytic cells of the liver. These cells separate the sporozoites from their cellular target, the hepatocyte, to which they do not have direct access from the blood. Inside the host hepatocyte, each sporozoite produces many thousands of merozoites, each of which potentially can initiate infection in the blood by invading an erythrocyte. Despite the wealth of information available on the biology of the sporozoite and hepatic life-cycle stages of Plasmodium, details of how sporozoites cross the sinusoidal cell layer and its basement membrane to reach their target cell have remained unsatisfactorily vague.Invasion of host cells by intracellular microbial pathogens, bacteria and apicomplexan protozoan parasites typically occurs without disruption to the plasma membrane of the host cell and is accompanied by the encapsulation of the infectious agent within a membrane-bound vacuole. Now, Mota et al.1xMigration of Plasmodium sporozoites through cells before infection. Mota, M.M et al. Science. 2001; 290: 141–144Crossref | Scopus (277)See all References1 have shown that Plasmodium sporozoites possess an alternative mechanism of entry into mammalian cells that flouts biological convention by directly penetrating the host cell's plasma membrane. After the plasma membrane has been breached by Plasmodium yoelii or Plasmodium falciparum sporozoites it reseals rapidly, which is necessary for host cell survival. Using time-lapse video microscopy and standard cell biology assays, this was observed equally in mammalian hepatoma, epithelial and fibroblast cells. By this means, sporozoites might pass through up to four cells before forming a vacuole to allow cell entry at the surface of the hepatocyte in which they later develop and replicate. Importantly, liver cells from P. yoelii-infected mice showed signs of puncture wound repair, suggesting that this is not an in vitro artifact.Shortly after the initiation of infection, in vitro and in vivo observations of sporozoites from Plasmodium and Eimeria have shown that they lack a parasitophorous vacuole when inside the cytoplasm of the host cell. This was difficult to explain in the context of apicomplexan infection because the development of intracellular parasites has always been seen within a clearly delineated parasitophorous vacuole. The findings of Mota et al.1xMigration of Plasmodium sporozoites through cells before infection. Mota, M.M et al. Science. 2001; 290: 141–144Crossref | Scopus (277)See all References1 appear to reconcile these apparently discrepant observations. Eimeria and Toxoplasma sporozoites are also known to enter and exit cultured cells, indicating that the ability to migrate through host cells before infecting one of them is common to perhaps all apicomplexan parasites.The capacity of Plasmodium sporozoites to traverse non-specific mammalian cells raises questions about the importance of this process to malaria infection and the mechanisms used to actively disrupt the plasma membrane, to move across cytoplasm and to repair cell wounding. Mota et al.1xMigration of Plasmodium sporozoites through cells before infection. Mota, M.M et al. Science. 2001; 290: 141–144Crossref | Scopus (277)See all References1 speculate that a sporozoite might need to cross several cells in the search for a hepatocyte receptive to infection or to activate signalling pathways necessary for entering and developing within a given hepatocyte. The migration of sporozoites through cells is probably essential to the successful development of the malaria parasite in the liver.