Plasmodium falciparum sexual parasites develop in human erythroblasts and affect erythropoiesis
- 16 September 2020
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 136 (12), 1381-1393
- https://doi.org/10.1182/blood.2019004746
Abstract
Plasmodium falciparum gametocytes, the sexual stage responsible for malaria parasite 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 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.This publication has 48 references indexed in Scilit:
- The extravascular compartment of the bone marrow: a niche for Plasmodium falciparum gametocyte maturation?Malaria Journal, 2012
- A switch in infected erythrocyte deformability at the maturation and blood circulation of Plasmodium falciparum transmission stagesBlood, 2012
- Proof of principle for transfusion of in vitro–generated red blood cellsBlood, 2011
- Protein Export Marks the Early Phase of Gametocytogenesis of the Human Malaria Parasite Plasmodium falciparumMolecular & Cellular Proteomics, 2010
- A flow cytometry‐based assay for measuring invasion of red blood cells by Plasmodium falciparumAmerican Journal of Hematology, 2010
- Stage-specific susceptibility of human erythroblasts to Plasmodium falciparum malaria infectionBlood, 2009
- Soluble factors from Plasmodium falciparum-infected erythrocytes induce apoptosis in human brain vascular endothelial and neuroglia cellsMolecular and Biochemical Parasitology, 2008
- An In Vivo and In Vitro Model of Plasmodium falciparum Rosetting and Autoagglutination Mediated by varO , a Group A var Gene Encoding a Frequent SerotypeInfection and Immunity, 2008
- Behavioral changes induced by Toxoplasma infection of rodents are highly specific to aversion of cat odorsProceedings of the National Academy of Sciences of the United States of America, 2007
- Human Malaria Parasites in Continuous CultureScience, 1976