All vector mosquito species must feed on the blood of a vertebrate host to produce eggs. Multiple cycles of blood feeding also promote frequent contacts with hosts, which enhance the risk of exposure to infectious agents and disease transmission. Blood feeding triggers the release of insulin-like peptides (ILPs) from the brain of the mosquito Aedes aegypti, which regulate blood meal digestion and egg formation. In turn, hemocytes serve as the most important constitutive defense in mosquitoes against pathogens that enter the hemocoel. Prior studies indicated that blood feeding stimulates hemocytes to increase in abundance, but how this increase in abundance is regulated is unknown. Here, we determined that phagocytic granulocytes and oenocytoids express the A. aegypti insulin receptor ( AaMIR). We then showed that: 1) decapitation of mosquitoes after blood feeding inhibited hemocyte proliferation, 2) a single dose of insulin-like peptide 3 (ILP3) sufficient to stimulate egg production rescued proliferation, and 3) knockdown of the AaMIR inhibited ILP3 rescue activity. Infection studies indicated that increased hemocyte abundance enhanced clearance of the bacterium Escherichia coli at lower levels of infection. Surprisingly, however, non-blood fed females better survived intermediate and high levels of E. coli infection than blood fed females. Taken together, our results reveal a previously unrecognized role for the insulin signaling pathway in regulating hemocyte proliferation. Our results also indicate that blood feeding enhances resistance to E. coli at lower levels of infection but reduces tolerance at higher levels of infection.
Mosquitoes are vectors of several important diseases of humans and other mammals including Dengue fever, malaria and filariasis. These diseases adversely affect worldwide health by killing or debilitating millions of individuals. The key feature of mosquito biology that makes them such important disease vectors is that adult females must feed on the blood of their vertebrate host(s) to produce eggs. In turn, repeated bouts of blood feeding and egg development elevate the risk of mosquitoes feeding on an infected host and transmitting a given pathogen from one individual to another. A key regulator of egg development following blood feeding is the release of insulin-like peptides from the mosquito brain. We have found that insulin-like peptides enhance production of immune cells (hemocytes) that serve as the first line of defense against infection. Conversely, the molecular pathways that regulate egg development and hemocyte proliferation reduce the ability of mosquitoes to tolerate a persistent systemic infection. Taken together, our results indicate that trade-offs exist between reproduction and immune defense in mosquitoes, which is a subject of fundamental interest to evolutionary biologists and of applied importance in understanding disease transmission.