Innate immune signaling in Drosophila melanogaster shifts lipid metabolism to support immune function
Martinez, Brittany, Pharmacology - School of Medicine, University of Virginia
Bland, Michelle, MD-PHAR Pharmacology, University of Virginia
In a well-fed, healthy animal, insulin signaling drives nutrient storage and growth. Stressors to the system, such as starvation, lead to breakdown of stored energy to promote survival. Many animals undergo stress due to nutrient shortage or life stage. Bears hibernate, many birds migrate, and some insects go through metamorphosis; all of these life stages require the animal to prepare for nutrient shortage. In the wild, animals must overcome stressors in order to survive, such as infection or even unresolved inflammation due to aberrant activation of the immune system that reroutes energy to fight invading organisms. During infection, cellular resources are allocated toward the metabolically-demanding processes of synthesizing and secreting effector proteins that neutralize and kill invading pathogens. In Drosophila melanogaster, these effectors are antimicrobial peptides that are produced in the fat body, an organ that also serves as a major lipid storage depot. This dissertation addresses how activation of Toll signaling in the larval fat body perturbs lipid homeostasis to understand how cells meet the metabolic demands of the immune response. This work endeavors to explain how changes in anabolic lipid metabolism support the immune response and the detrimental outcomes that occur during acute infection if the metabolic changes can no longer be met. Specifically, the data presented show a metabolic shift from triglyceride storage to phospholipid synthesis in order to promote survival during infection. This work adds to the growing field of immunometabolism to provide insight into the mechanisms of lipid changes during chronic immune activation. Importantly, these studies are performed in an in vivo system to study whole-animal physiology as well as effects within tissues dedicated to nutrient storage and immune effector synthesis.
PHD (Doctor of Philosophy)
Drosophila melanogaster, immunity, metabolism, lipid metabolism, immunometabolism, Toll signaling, fruitfly