Apoptosis and immunity: Characterizing the cell death machinery in the yellow fever mosquito, Aedes aegypti

Mosquito-borne viruses represent some of the most devastating of the emerging infectious diseases. The Dengue viruses (DENv) that cause Dengue Fever, Dengue Hemorrhagic Fever and Dengue Shock Syndrome are examples of epidemic re-emerging human diseases. There are no vaccines available for DENv; and control programs rely on reducing populations of the principle vector, Aedes aegypti. Novel control strategies are essential and these will rely on a mechanistic understanding of the molecular and biochemical interactions between vectors and pathogens. While we have made great advances in our understanding of insect antibacterial and antiparasite defence mechanisms, the study of antiviral defences in insect vectors has lagged behind.;Apoptosis was detected in midgut tissues of Ae. aegypti challenged with DENv. During the early stages of infection, we detected an up-regulation of the pro-apoptotic caspase, Aedronc. Subsequently, as Aeiap1 transcripts increased, apoptosis declined. We hypothesize that apoptosis in midguts during virus invasion represents a host response to clear virus-infected cells, and suggest this process is mediated by AeIAP1. Whether the increase in Aeiap1 is a host-mediated signal or a viral strategy to limit the clearance of apoptotic cells will be the subject of further research.;Deciphering the mechanisms that enable insects to cope with infections is essential to our understanding of innate immunity and may influence our current understanding of how apoptosis fits into the antiviral defence strategies used by both vertebrates and invertebrates.;Keywords. apoptosis; caspases; FADD adaptors; IAPs; Dengue virus, Aedes aegypti; insect immunity.;Apoptosis is an antiviral response characterized in many organisms. The work presented here provides some basic information about the apoptotic machinery in Aedes aegypti, and establishes a role for apoptosis in various aspects of mosquito immunity. We describe the characterization four apoptosis-related genes; two initiator caspases, one caspase adaptor, and one inhibitor of apoptosis protein, which provides evidence for the conservation of cell death pathways in mosquitoes. The two initiator caspases, AeDronc and AeDredd, are involved primarily in development and immune signaling pathways, respectively. The caspase adaptor, AeFADD, interacts with AeDredd in-vitro, and also functions as part of the IMD antimicrobial immune signaling pathway. The Inhibitor of Apoptosis molecule (AeIAP1) provides a pro-survival signal to prevent unwanted cell death.