Fat on the frontline: Immune control of energy stores during infection

Immune responses are energetically demanding, making it surprising that organisms suppress food intake (anorexia) and use endogenous energy stores to fuel immune responses to chronic infection, resulting in weight loss. Infection with the parasite Trypanosoma brucei leads to anorexia, weight loss and reductions in white adipose tissue (WAT) mass, making it an ideal model for understanding this phenomenon. I recently discovered that during this infection the cytokine interleukin 17 (IL-17), drives anorexia and reductions in bodyweight/WAT mass. To understand how infection and IL-17 alter metabolic adaptation to infection, I will define alterations in whole-body metabolism. Using cutting-edge technologies and genetic deletion models, I will characterise the WAT to understand how stromal cells, adipocytes, and immune cells interact to induce tissue wasting during infection and control local pathogen burden. To determine what drives anorexia, I will examine adipokine signalling in the brain during infection. Together, this project will result in a greater understanding of how immune factors drive metabolic changes during infection, leading to changes in physiology and behaviour. This information could ultimately be exploited for intervention and treatment of a range of diseases involving weight loss and anorexia, including HIV and cancer and could open new paths to obesity treatments.