Evidencing the Role of Erythrocytic Apoptosis in Malarial Anemia

Abstract

In the last decade it has become clear that, similarly to nucleated cells, enucleated red blood cells (RBCs) are susceptible to programmed apoptotic cell death. Erythrocytic apoptosis seems to play a role in physiological clearance of aged RBCs, but it may also be implicated in anemia of different etiological sources including drug therapy and infectious diseases. In malaria, severe anemia is a common complication leading to death of children and pregnant women living in malaria-endemic regions of Africa. The pathogenesis of malarial anemia is multifactorial and involves both ineffective production of RBCs by the bone marrow and premature elimination of non-parasitized RBCs, phenomena potentially associated with apoptosis. In the present overview, we discuss evidences associating erythrocytic apoptosis with the pathogenesis of severe malarial anemia, as well as with regulation of parasite clearance in malaria. Efforts to understand the role of erythrocytic apoptosis in malarial anemia can help to identify potential targets for therapeutic intervention based on apoptotic pathways and consequently, mitigate the harmful impact of malaria in global public health.

Keywords: anemia; apoptosis; malaria; phagocytosis; red blood cells.

Figure 1

Model of erythrocytic apoptosis involvement in the pathogenesis of malarial anemia. Both parasitic antigens and host factors modulated by malaria infection generate a favorable environment for precocious induction of erythrocytic apoptosis (black arrows), which can be enhanced by antimalarial drug treatment, and in the case of parasitized red blood cells (pRBCs), by intraerythrocytic parasite development. Erythrocytic apoptosis provokes cellular changes, i.e., cell rigidity increase, exposure of phosphatidylserine and downexpression of CD47, that drive pRBC (white arrows) and non-parasitized RBC (nRBC; gray arrows) to phagocytosis. Elimination of apoptotic nRBCs along with pRBC lysis and erythropoiesis impairment contribute to the development of malarial anemia. Uptake of apoptotic pRBCs can help control parasite load. In this manner, the pathogenic or protective role of erythrocytic apoptosis in malaria could be a result of increased apoptosis induction differentially in nRBC and pRBC, respectively.