Date of Award
Doctor of Philosophy
Ryan C Smith
Most mosquitoes rely on a blood meal to acquire the nutrients necessary for egg development. This blood-feeding behavior exposes mosquitoes to blood-borne pathogens, such as malaria; a deadly disease caused by Plasmodium parasites and transmitted by Anopheles mosquitoes. Arguably the most effective malaria prevention techniques target the mosquito vector. Here, we expand the current understanding of mosquito immunity to Plasmodium parasites. Specifically, we investigate whether the steroid hormone, 20-hydroxyecdysone (20E) influences anti-Plasmodium immunity. Given that levels of 20E peak at approximately the same time that Plasmodium parasites migrate through the gut walls of Anopheles mosquitoes, studies have suggested that 20E is important for preventing malaria survival. Here, we demonstrate that 20E injection stimulates cellular immunity and significantly reduces P.berghei survival. To validate these results, we targeted the Halloween gene family using RNAi with the goal of reducing ecdysone production. We determined that the standard concentration of dsRNA was not adequate to keep expression levels reduced following blood-feeding. In agreement with previous work, we demonstrate that 20E agonists can prime anti-Plasmodium immunity. Furthermore, we identify temporally when halofenozide influences parasite survival and demonstrate that the 20E canonical receptor is required for halofenozide primed anti-Plasmodium immunity. The final chapter diverges from studying 20E and instead asks whether multiple blood meals taken by a mosquito during parasite development influences parasite survival. Ultimately, we found that multiple blood meals reduce P. berghei survival but do not affect P. falciparum survival, suggesting that P. falciparum parasites have adapted to their natural mosquito host which likely takes multiple meals under natural conditions. Together, the findings presented here provide an expanded understanding of mosquito anti-Plasmodium immunity and may prove beneficial for development of novel malaria prevention tools.
Rebekah Ann Reynolds
Reynolds, Rebekah Ann, "Novel insights into a well-studied steroid hormone: The impacts of 20-hydroxyecdysone (20E) on mosquito immunity" (2020). Graduate Theses and Dissertations. 18206.