Mounting an immune response is a nutritionally demanding process that requires systemic redistribution of energy stores. Cytokine-induced insulin resistance serves as a mechanism that simultaneously induces the mobilization of lipids and carbohydrates and limits their consumption by tissues not directly involved in the immune response. However, the basic metabolic needs of vital organs and tissues must be met with alternative fuels to maintain their functionality.

In this project, we employ Drosophila melanogaster to investigate the role of ketone bodies as an alternative energy source during severe bacterial infection accompanied by insulin resistance and associated metabolic stress. We observe that infection leads to increased expression of genes controlling ketogenesis in the fat body and macrophages. Although increased production of ketone bodies by the fat body or macrophages is not necessary to limit pathogen growth and bacterial burden, it is still essential for the survival of infections. While the production of ketone bodies from the fat body is used as nutritional support for neurons and substantially reduces infection-induced autophagy in these cells, the role of macrophage-produced ketone bodies in the context of infection needs to be addressed in future research.