Ruxolitinib protects glucocorticoid receptor knockout mice from lethal malaria-induced hypoglycemia

ABSTRACT: Disease tolerance is a key defense mechanism that limits damage to the host without directly reducing pathogen levels. In malaria, these mechanisms are essential for preventing severe disease and death but remain poorly understood. In this study, we show that glucocorticoid receptor (GR)-mediated processes play a vital role in disease tolerance during Plasmodium chabaudi AS infection. GR deletion in infected mice resulted in lethal hypoglycemia and a cytokine storm. Hypoglycemia was driven by severe metabolic dysfunction in liver and spleen, characterized by increased glucose uptake, glycogen depletion, a dominant glycolytic profile and reduced gluconeogenic gene expression. Importantly, this hypoglycemic state was strongly associated with overactivation of the JAK/STAT pathway and excessi

SUBMITTER: Fran Prenen 

PROVIDER: S-SCDT-10_1038-S44321-025-00264-W | biostudies-other |

REPOSITORIES: biostudies-other