The interrelation between endogenous glucocorticoids, inflammation and metabolic disturbances in malaria

Yearly, almost half a million of people die from malaria, a global parasitic disease. The mechanisms that explain why some people progress from uncomplicated to complicated malaria remain poorly characterized and this impedes the development of novel treatments. Disease tolerance mechanisms promote survival by limiting the pathological consequences of the infection without interfering with parasite load. In our recent study, we revealed that adrenal hormones confer disease tolerance in malaria by preventing excessive inflammation and hypoglycemia, suggesting a link between metabolism and immune responses in malaria. The hypothesis of this interdisciplinary project is that immune responses during malaria are associated with metabolic disturbances such as hypoglycemia and that this balance is maintained by endogenous glucocorticoids. In this project, I will detail the in vivo mechanisms by which adrenal hormones – and more specifically glucocorticoids – restrain inflammation and glucose consumption. These insights will be validated in malaria patients in a unique high endemic setting with excellent research facilities. Furthermore, state-of-the-art technologies will be applied, in collaboration with renowned experts. Better understanding of the vastly understudied metabolic disturbances during malaria in relation to immune reactions and endogenous glucocorticoids might lead to the development of new adjuvant therapies for the highly lethal complications of malaria