Reticulocyte Infection Leads to Altered Behaviour, Drug Sensitivity and Host Cell Remodelling by Plasmodium falciparum

Plasmodia are host-specific, both at the organism and cellular levels. During asexual development, infect cells of erythroid lineage, with an overall propensity towards reticulocytes. This applies to even , the most common causative agent of human malaria, implications of which remain unexplored. Herein, for the first time, we characterize the developmental stages and features of cultured in young reticulocytes (CD71) in comparison to standard normocyte (CD71) cultures. We demonstrate that there are notable differences in the patterns of invasion, development and sensitivity to potent antimalarials (such as artemisinin and dihydroartemisinin) for parasites residing in CD71 reticulocytes. Through a transcriptomic approach, we report that parasites are able to sense the host cell environment, and calibrate their metabolic and host cell remodelling pathways through differential gene expression. These results form an exciting avenue on which hitherto unexplored interactions between and different stages of host red blood cells could be investigated in the broader contexts of drug resistance, host tropism and zoonosis.