Targeting the IL33–NLRP3 axis improves therapy for experimental cerebral malaria

Significance Cerebral malaria (CM) is a neurological complication of malaria infection that, despite antimalarial drug treatment, results in fatality or neurodisability in approximately 25% of cases. Thus, there is an urgent clinical need to develop therapies that can improve the efficacy of antimalarial drugs to prevent or reverse cerebral pathology. Here, we show in an experimental mouse model of CM (ECM) that IL33 administration can improve survival and reduce pathology in the brain over antimalarial drugs alone. Mechanistically, we demonstrate that IL33 enhances recovery from ECM by inhibiting NLRP3 inflammasome-induced inflammatory responses within the brain. These results suggest that IL33 and NLRP3 inflammasome inhibitors may be effective adjunctive therapies for CM.