Plasmodium Infection–Cure Cycles Increase the Capacity of Phagocytosis in Conventional Dendritic Cells

Malaria stands as one of the most pervasive human infectious diseases globally and represents a prominent cause of mortality. Immunity against clinical malaria disease is achieved through multiple infection and treatment cycles, culminating in a substantial reduction in parasite burden. To investigate this phenomenon, we established a murine model involving repeated infection–cure cycles, whereby mice were infected with the lethal rodent malarial parasite Plasmodium berghei ANKA and subsequently treated with the anti-malarial drug pyrimethamine. Our earlier study revealed a significant decrease in the capacity of conventional dendritic cells (cDCs) to produce cytokines upon stimulation in infection-cured mice. In the present study, we aimed to further elucidate the modulation of cDC functionality during repeated infection–cure cycles by examining their phagocytic capacity. Administering fluorescent beads to mice resulted in no significant difference in the total number of bead-positive cells within the spleens of both uninfected and 3-cure (three cycles of infection–cure) mice. However, the proportion of the CD11c(+)F4/80(−) population within bead-positive cells was notably higher in 3-cure mice compared to uninfected mice. Subsequent in vitro analysis of bead phagocytosis by purified CD11c(+)cDCs revealed that the cDC2 subset from 3-cure mice exhibited significantly enhanced phagocytic capacity in comparison to their uninfected counterparts. These findings underscore the substantial impact of repeated infection–cure cycles on various facets of cDC function, potentially influencing the trajectory of immune responses against subsequent malaria infections.