Glucocorticoid regulation of systemic immunometabolism in malaria

Malaria is a parasitic disease that poses a major health threat to the world with an estimated 219 million cases and 435000 deaths in 2017. Especially the complications of malaria are life-threatening and have ~15% fatality rates despite antimalarial treatment.  These complications include amongst others cerebral malaria, severe anemia and respiratory problems and are further worsened by metabolic disturbances, such as hypoglycemia and hyperlactatemia. Protection against malaria relies on immune mechanisms to limit the parasite proliferation, and on so-called disease tolerance mechanisms which are essential to maintain systemic homeostasis. In this project, we will investigate how glucocorticoids interact with the immune system and with the central carbon metabolism to maintain and optimize systemic metabolic homeostasis during this life-threatening infection. State-of-the-art technologies will be applied to study these regulatory systems in mouse models of malaria and in patients from endemic regions. Overall, this project will provide a novel integrative concept of the function of glucocorticoids in infection and will reveal new insights that will provide novel clues for improved therapy of malaria.