Abstract
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.