Circadian control of the innate immune response to plasmodium infection 4542

Abstract Description Malaria is a mosquito-borne disease caused by infection with the parasite Plasmodium. In the human host Plasmodium first infects hepatocytes, and then red blood cells (RBCs). Infected red blood cells synchronously burst every 24-72 hours depending on the Plasmodium species, causing rhythmic fevers in the host. For some time, it was believed that malaria’s rhythmic effects were solely in response to the hosts circadian clocks; however, it was recently shown that in an arrhythmic host, malaria parasites retain rhythmicity while individual parasites lose synchrony to each other over time. These results suggest that parasites have intrinsic clocks and that an unknown host cue drives parasites to burst synchronously from RBCs. It is well documented that the innate immune response is under circadian control. Additionally, malaria parasites have evolved to adhere to blood vessels possibly to avoid clearance through the spleen; however, whether rhythms in innate immune cells are essential for controlling infection remains unresolved. We show that rhythms in the innate immune compartment are well defined during infection with P. chabaudi, as shown by both cell numbers and cytokine levels. To our surprise however, these rhythms persist in the absence of cell intrinsic clocks in myeloid derived cells. This suggests, that although immune rhythms are enhanced during infection, they are likely the consequence, not the cause, of the rhythmic and synchronous bursting of red blood cells. Funding Sources 2024 Sidney MacDonald Russell Fellowship Fellow; Immunology and Molecular Medicine T32 Training Grant; HHMI Emerging Pathogens Initiative Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)