Abstract:

Malaria remains a global health problem, often associated with numerous red blood cell defects, such as anemia. Despite the successful efforts to control malaria in many areas of the world, the important role played by malaria infection in anemia remains poorly researched. Malaria is caused by infection of red blood cells by Plasmodium parasites. There has been evidence that Plasmodium falciparum parasites accumulate in patient tissues such as the bone marrow parenchyma, where the erythroid differentiation occurs, suggesting that malaria parasites may interfere with erythropoiesis. Accordingly, previous studies reported that extracellular vesicles (EVs) secreted by P. falciparum infected erythrocytes can influence red blood cell differentiation in vitro. Here, we also provide evidence of delay of erythropoiesis in vitro by EVs purified from plasma of P. falciparum infected children from Benin. However, the molecular identity of the factor(s) in the EVs that drive impaired erythropoiesis and their human target(s) remain to be identified. We, therefore, address the mechanism of inhibition of erythropoiesis mediated by EVs from P. falciparum infected erythrocytes. We performed proteomics analysis of EVs to select parasite candidate proteins likely to play a role in the erythropoiesis delay. Heterologous expression of one of these candidates in hematopoietic stem line was sufficient to inhibit cell proliferation. Expression of the tagged protein allowed to perform localization studies in erythroblasts by confocal microscopy and immunoprecipitation of interacting partners. Understanding the mechanisms by which the parasite influences its hosts is crucial for improving our tools against the numerous blood related deficiencies that patients with malaria face even after their treatments.