Plasmodium falciparum sexual parasites develop in human erythroblasts and affect erythropoiesis

• Published in: Blood Vol. Online ahead of print; no. 12; pp. 1381 - 1393
• Main Authors: Neveu, Gaëlle, Richard, Cyrielle, Behera, Prativa Kumari, Volpe, Fiona, Dupuy, Florian, Subramani, Pradeep Annamalai, Marcel-Zerrougui, Benjamin, Vallin, Patrice, Andrieu, Muriel, Minz, Aruna Mukti, Azar, Nabih, Martins, Rafael, Lorthiois, Audrey, Gazeau, Florence, Lopez-Rubio, Jose-Juan, Mazier, Dominique, Silva, Amanda K.A., Satpathi, Sanghamitra, Verdier, Frédérique, Wassmer, Samuel, Lavazec, Catherine
• Format: Journal Article
• Language: English
• Published: American Society of Hematology 26-06-2020
• Subjects: Hematology; Human health and pathology; Life Sciences; Microbiology and Parasitology; Parasitology; Erythropoiesis; Iron; Red Cells
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2019004746

Plasmodium falciparum gametocytes, the sexual stages responsible for malaria parasites transmission from humans to mosquitoes, are key targets for malaria elimination. Immature gametocytes develop in the human bone marrow parenchyma, where they accumulate around erythroblastic islands. Notably though, the interactions between gametocytes and this hematopoietic niche have not been investigated. Here we identify late erythroblasts as a new host cell for P.falciparum sexual stages and show that gametocytes can fully develop inside these nucleated cells in vitro and in vivo, leading to infectious mature gametocytes within reticulocytes. Strikingly, we found that infection of erythroblasts by gametocytes and parasite-derived extracellular vesicles delay the erythroid differentiation, thereby allowing gametocyte maturation to coincide with the release of their host cell from the bone marrow. Taken together, our findings highlight new mechanisms that are pivotal for the maintenance of immature gametocytes in the bone marrow, and provide further insights on how Plasmodium parasites interfere with erythropoiesis and contribute to anemia in malaria patients.