Active migration and passive transport of malaria parasites

Abstract

Malaria parasites undergo a complex life cycle between their hosts and vectors. During this cycle the parasites invade different types of cells, migrate across barriers, and transfer from one host to another. Recent literature hints at a misunderstanding of the difference between active, parasite-driven migration and passive, circulation-driven movement of the parasite or parasite-infected cells in the various bodily fluids of mosquito and mammalian hosts. Because both active migration and passive transport could be targeted in different ways to interfere with the parasite, a distinction between the two ways the parasite uses to get from one location to another is essential. We discuss the two types of motion needed for parasite dissemination and elaborate on how they could be targeted by future vaccines or drugs.

Keywords: active migration; drug targeting; parasite dissemination; passive transport; vaccine design.

Figure 1.

Active movement and passive transport transitions along the Plasmodium life cycle. Stages of active migration (red arrows) and passive transport (blue arrows). Sporozoites emerge from the oocyst (1) and are passively transported within the hemolymph before actively migrating into the salivary glands (2). From there, they are passively ejected with the saliva and take up active motility again in the skin (3). Once they enter either the lymph or blood, again they are passively transported to actively enter either the lymph node or the liver parenchyma. Sporozoites that have entered the liver differentiate within a hepatocyte; following the development of exoerythrocytic forms, merosomes bud from the infected hepatocyte (4). After membrane rupture, merosomes release hundreds to thousands of merozoites into the blood that briefly are carried by the blood before attaching to and actively invading erythrocytes (5). Within the erythrocyte, schizogony results in more merozoites that then egress from cells. These merozoites are passively carried in the blood and, subsequently, actively invade nearby uninfected erythrocytes. Some merozoites actively invade and develop into male or female gametocytes that await transmission into the arthropod host (6). In the mosquito, gamete maturation results in actively-moving male gametes that fuse with females to produce a zygote (7). Zygotes develop into motile ookinetes that can actively traverse the mosquito peritrophic matrix and midgut epithelia (8) to establish oocysts in the basal lamina of the insect host.