2nd Place: Immune defense and the unfolded protein response in Aedes aegypti mosquitoes

Aedes aegypti are responsible for the spread of various disease-causing pathogens, causing millions of infections annually. Arthropod vectors like Ae. aegypti are unique in their ability to remain healthy during infection with pathogens that kill human hosts. This trait, known as immune tolerance, is relatively understudied despite being critical to pathogen transmission (i.e., mosquitoes must survive infections to transmit pathogens). In our previous work, we have found that blood feeding prior to bacterial infection significantly increases tolerance to infection in female Ae. aegypti. To further our understanding of the molecular signaling pathways that mediate immune tolerance in mosquitoes, we are investigating a signal transduction pathway that is induced by a blood meal, the Unfolded Protein Response (UPR). The UPR is a highly conserved cellular stress-mediating, homeostasis-promoting pathway implicated in a variety of biological functions associated with health, disease, and immunity. To explicate the role of the UPR in tolerance and immunity, we will, in parallel, 1) “turn on” the UPR pharmacologically using dithiothreitol, and 2) “turn off” the UPR using RNAi-mediated knockdown before intrathoracically infecting all treatment and control groups with E. coli S17. Post-infection, we will collect survival and bacterial load data across an infection timecourse. These data will be used to build binomial generalized linear models testing the effect of our UPR-modifying treatments on immune tolerance. In summary, we will assess potential interplay between the UPR, a highly conserved pathway relevant to homeostasis and immunity, and immune tolerance, an understudied mosquito trait critical to pathogen transmission.