Abstract
The midgut epithelium of the mosquito malaria vector Anopheles is a hostile environment for Plasmodium, with most parasites succumbing to host defenses. This study addresses morphological and ultrastructural features associated with Plasmodium berghei ookinete invasion in Anopheles gambiae midguts to define the sites and possible mechanisms of parasite killing. We show by transmission electron microscopy and immunofluorescence that the majority of ookinetes are killed in the extracellular space. Dead or dying ookinetes are surrounded by a polymerized actin zone formed within the basal cytoplasm of adjacent host epithelial cells. In refractory strain mosquitoes, we found that formation of this zone is strongly linked to prophenoloxidase activation leading to melanization. Furthermore, we identify two factors controlling both phenomena: the transmembrane receptor frizzled-2 and the guanosine triphosphate–binding protein cell division cycle 42. However, the disruption of actin polymerization and melanization by double-stranded RNA inhibition did not affect ookinete survival. Our results separate the mechanisms of parasite killing from subsequent reactions manifested by actin polymerization and prophenoloxidase activation in the A. gambiae–P. berghei model. These latter processes are reminiscent of wound healing in other organisms, and we propose that they represent a form of wound-healing response directed towards a moribund ookinete, which is perceived as damaged tissue.
Highlights
Few infectious diseases carry heavier economic and social burdens than malaria
In this study we examined the ultrastructure of P. berghei ookinete invasion of the A. gambiae midgut, and possible mechanisms of P. berghei killing by refractory mosquitoes
Our transmission electron microscopy (TEM) microscope studies consistently demonstrated that the ookinetes are predominantly located in the extracellular space, where they are exposed to hemocyte-derived soluble immunity factors, rather than in intracellular locations
Summary
Within Anopheles mosquitoes, the only natural vectors of human malaria, immune responses to the Plasmodium parasite are highly species and strain specific. The zygotes formed develop into motile, banana-shaped ookinetes, which invade and traverse the midgut epithelium approximately 24 h after blood ingestion (depending on the host–parasite species combination). During this trip the majority of ookinetes are destroyed by host responses even in susceptible mosquito strains, but a few surviving ookinetes reach the basal side of the midgut and transform into oocysts, which mature over the 10–12 d to release thousands of sporozoites into the mosquito hemocoel. Successful salivary gland sporozoites are transmitted to a new vertebrate host via an infective bite
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