Impact of increased insulin signaling in the fat body of Anopheles stephensi mosquitoes

Malaria is one of the world’s most prevalent diseases. There are over 200 million annual clinical cases reported, and an estimated 660,000 deaths due to malaria. Of these fatalities, 77% are children under the age of five years. In spite of current efforts to control malaria, the appearance of insecticide-resistant mosquitoes and drug-resistant parasite continues to accelerate the crisis of malaria transmission worldwide. Therefore, there is an urgent need for new innovative strategies to ease this burden. One strategy is to genetically engineer mosquitoes with better fitness and less parasites susceptible to replace the wild population. In mosquitoes, the insulin/insulin growth factor 1 signaling (IIS) cascade regulates lifespan, reproduction, and innate immunity. To better understand the impact of IIS in mosquitoes, we induced IIS in the fat body of transgenic A. stephensi mosquitoes by expressing an active form of A. stephensi Akt (AnsteAkt), a key component of the IIS cascade. The mosquito’s fat body is the main tissue responsible for antimicrobial production and has been shown to serve as “signaling center” for IIS pathway. In early studies we found that Myr-AnsteAkt transcript and protein expression occurred in a fat body and blood meal specific manner, as expected for a transgene regulated by the vitellogenin promoter. Furthermore, we have been able to demonstrate increased activation of downstream IIS molecules indicating activation of the IIS cascade. We also observed changes in vitellogenin protein levels, but surprisingly did not observe any change in egg production. Most importantly, we observed a significant extension in the lifespan of the myr-AsteAkt transgenic A. stephensi. This increase in lifespan opens intriguing possibilities for manipulating the fitness of transgenic parasite resistant mosquitoes.