Examining the Reticulocyte Preference of Two Strains during Blood-Stage Malaria Infection.

The blood-stage of the parasite is one of the key phases within its life cycle that influences disease progression during a malaria infection. The efficiency of the parasite in infecting red blood cells (RBC) determines parasite load and parasite-induced hemolysis that is responsible for the development of anemia and potentially drives severe disease progression. However, the molecular factors defining the infectivity of parasites have not been completely identified so far. Using the mouse model for malaria, we characterized and compared the blood-stage infection dynamics of ANKA WT and a mutant parasite strain lacking a novel antigen, maLS_05, that is well conserved in both human and animal parasite strains. Infection of mice with parasites lacking leads to lower parasitemia levels and less severe disease progression in contrast to mice infected with the wildtype ANKA strain. To specifically determine the effect of deleting on parasite infectivity we developed a mathematical model describing erythropoiesis and malarial infection of RBC. By applying our model to experimental data studying infection dynamics under normal and drug-induced altered erythropoietic conditions, we found that both ANKA and (-) parasite strains differed in their infectivity potential during the early intra-erythrocytic stage of infection. Parasites lacking showed a decreased ability to infect RBC, and immature reticulocytes in particular that are usually a preferential target of the parasite. These altered infectivity characteristics limit parasite burden and affect disease progression. Our integrative analysis combining mathematical models and experimental data suggests that deletion of affects productive infection of reticulocytes, which makes this antigen a useful target to analyze the actual processes relating RBC preferences to the development of severe disease outcomes in malaria.