Malaria parasite pre-erythrocytic stage infection: gliding and hiding

Abstract

In malaria, the red blood cell-infectious form of the Plasmodium parasite causes illness and the possible death of infected hosts. The initial infection in the liver caused by the mosquito-borne sporozoite parasite stage, however, causes little pathology and no symptoms. Nevertheless, pre-erythrocytic parasite stages are attracting passionate research efforts not least because they are the most promising targets for malaria vaccine development. Here, we review how the infectious sporozoite makes its way to the liver and subsequently develops within hepatocytes. We discuss the factors, both parasite and host, involved in the interactions that occur during this "silent" phase of infection.

Figure 1. The sporozoite journey to the hepatocyte and subsequent liver stage development: parasite and host interactions

The infectious sporozoite is deposited into the skin and subsequently enters the bloodstream through a capillary endothelium (CE). A number of sporozoites also enter draining lymph nodes and can partially develop within the lymphoid endothelium (LE). Once in the liver sinusoid, sporozoites traverse a resident Kupffer cell (KC) to cross the fenestrated sinusoidal epithelium (SE). The sporozoite then traverses a number of hepatocytes before invading a hepatocyte with the formation of a parasitophorous vacuole membrane (PVM). Massive replication and growth lead to the formation of erythrocyte-infectious merozoites that enter the sinusoid packaged in extrusomes/merosomes and are subsequently released in the bloodstream. The parasite and host proteins known to be involved in this process are listed under the appropriate location and a timeline for the whole process for rodent parasites and human parasites (post infection, PI) is depicted at the base of the figure. Those proteins not referred to in the text are apical membrane antigen-1 (AMA1) and thrombospondin-related sporozoite protein (TRSP).