doi:10.1016/j.gde.2006.06.012
Copyright © 2006 Elsevier Ltd All rights reserved.
The developmental migration of Plasmodium in mosquitoes
Dina Vlachoua,
, Timm Schlegelmilcha, Ellen Runna, Antonio Mendesa and Fotis C. Kafatosa
aDivision of Cell and Molecular Biology, Faculty of Natural Sciences, Imperial College London, London, SW7 2AZ, UK
Available online 21 June 2006.
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Migration of the protozoan parasite Plasmodium through the mosquito is a complex and delicate process, the outcome of which determines the success of malaria transmission. The mosquito is not simply the vector of Plasmodium but, in terms of the life cycle, its definitive host: there, the parasite undergoes its sexual development, which results in colonization of the mosquito salivary glands. Two of the parasite's developmental stages in the mosquito, the ookinete and the sporozoite, are invasive and depend on gliding motility to access, penetrate and traverse their host cells. Recent advances in the field have included the identification of numerous Plasmodium molecules that are essential for parasite migration in the mosquito vector.
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Figure 1. Plasmodium migration in the mosquito host. The developmental lifecycle of Plasmodium in the mosquito starts with a female mosquito bite and blood meal on a malaria-infected vertebrate host; it ends with a new bite approximately three weeks later. Soon after blood feeding, ingested parasite gametocytes produce male and female gametes that fertilise and form the zygotes. Still in the gut lumen, the zygotes transform into motile ookinetes. Approximately one day after blood feeding, the ookinetes traverse the midgut epithelium; the invaded epithelial cells become apoptotic and are extruded from the midgut epithelium. Mosquito immune reactions result in processes, such as lysis and melanisation, mainly mediated by proteins that are present in the mosquito hemolymph. These processes drastically reduce the number of ookinetes that successfully develop to the next parasite stage, the oocyst, on the basal side of the epithelium. Approximately two weeks later — this length of time depends on the parasite–mosquito species combination — multiple nuclear divisions within each oocyst are followed by membrane partitioning and budding off of several thousand haploid sporozoites. Upon oocyst burst, this army of sporozoites is released into the haemocoel; many reach and infect the median and the distal lateral salivary gland lobes. Invasion of the salivary gland epithelial cells is thought to occur through the formation of a parasitophorous vacuole, following the interaction of sporozoites with the basal lamina and invagination of the host cell plasmalemma. A similar parasitophorous vacuole is formed around the sporozoites during their escape from the salivary glad cells into the secretory cavity of the glands. The final act of the parasites in the mosquito is the breakdown of this second vacuole and migration of sporozoites into the salivary ducts, from where they are ejected into a new vertebrate host upon the next mosquito bite.
Figure 2. Invasion of mosquito epithelia by Plasmodium parasite stages. Transgenic P. berghei parasites expressing green fluorescent protein (green) [17• and 71] are used for live in vivo confocal imaging of infected mosquito midgut (a) and salivary gland (b) tissues. The epithelial cell membranes are stained with a lipophilic vital dye (red and blue colours) as described [17•]. The magnification is increasing in the different panels, from left to right.