Abstract
Plasmodium falciparum gametocytes, the sexual stages responsible for malaria parasite transmission, develop in the human bone marrow parenchyma in proximity to the erythroblastic islands. Yet, mechanisms underlying gametocytes interactions with these islands are unknown. Here, we have investigated whether gametocyte-infected erythrocytes (GIE) adhere to erythroid precursors, and whether a putative adhesion may be mediated by a mechanism similar to the adhesion of erythrocytes infected with P. falciparum asexual stages to uninfected erythrocytes. Cell-cell adhesion assays with human primary erythroblasts or erythroid cell lines revealed that immature GIE do not specifically adhere to erythroid precursors. To determine whether adhesion may be dependent on binding of STEVOR proteins to Glycophorin C on the surface of erythroid cells, we used clonal lines and transgenic parasites that overexpress specific STEVOR proteins known to bind to Glycophorin C in asexual stages. Our results indicate that GIE overexpressing STEVOR do not specifically adhere to erythroblasts, in agreement with our observation that the STEVOR adhesive domain is not exposed at the surface of GIE.
Highlights
The spread of malaria in population relies on the ability of the Plasmodium parasites to be transmitted from infected individuals to mosquito vectors
We hypothesized that the adhesion of STEVORs to Glycophorin C (GPC) might contribute to sequestration of immature gametocytes in the bone marrow parenchyma by promoting adhesion of immature gametocyte-infected erythrocytes (GIE) to erythroblasts
The presence of immature gametocytes near the erythroblastic islands in extravascular spaces of bone marrow suggests a direct adhesion of immature GIE to the developing erythroblasts
Summary
The spread of malaria in population relies on the ability of the Plasmodium parasites to be transmitted from infected individuals to mosquito vectors. The unveiling of the hidden sites for gametocytes maturation raised the questions how these parasite stages develop and sequester in the bone marrow micro-environment and how they interact with the erythroblastic islands. Their presence in the bone marrow extra-vascular compartment and the absence of P. falciparum erythrocyte membrane protein 1 (PfEMP1) expression in gametocytes[6] suggest that gametocytes sequester via different mechanisms than those of asexual stages, which depend on cytoadhesion of infected erythrocytes to vascular endothelium through the interaction of PfEMP1 with endothelial receptors[7,8]. Our results show that GIE overexpressing STEVOR do not adhere to erythroblasts, and that STEVOR adhesive domain is not exposed at the surface of GIE
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