Changes in ADAR1 activity duringPlasmodiuminfection contribute to protection from malaria

Abstract

SummaryAdenosine deaminase acting on RNA 1 (ADAR1) suppresses the activation of multiple antiviral immune response pathways. Here, we investigate the role of ADAR1 during infection with thePlasmodiumparasite, which causes malaria and is responsible for over almost a half million childhood deaths every year. Reduced activity of ADAR1 duringPlasmodiuminfection is associated with populations protected from clinical malaria. In animal models,Adar+/-mice are protected fromP. yoeliiparasitemia, via a previously unreported pathway. These mice display elevated Type-I IFN responses and CD8+T cell activation, but no detrimental immune responses. Our results suggest that a decrease in the levels of ADAR1 occurs during infection and can drive both innate and adaptive immune responses, and this presents a previously unrecognized opportunity for targeting ADAR1 in diverse infectious diseases.