Dissection of the human bone marrow environment as a privileged niche for Plasmodium falciparum gametocyte development

Plasmodium falciparum gametocytes develop in the human host in 10-12 days and only mature stage V can be found in the peripheral circulation. Observations from histological studies of a systematic organ survey in pediatric cases of fatal malaria (1) and from an analysis of bone marrow samples from anemic children infected by P. falciparum (2) revealed that immature gametocytes accumulate in the human bone marrow and that they are readily observed in the extravascular sites of this organ, altogether putting the human bone marrow under the spotlight as a privileged niche for gametocyte maturation and for having a key role in human-to-mosquito transmission of the malaria parasites. The mechanism(s) driving gametocyte sequestration in the human bone marrow and which parasite sexual stage is involved in homing are unclear. As in vitro systems recapitulating the complexity of human bone marrow are presently missing, a Bone Marrow Humanized Mouse (BMHM) model based on osteoprogenitor cell transplantation has been established (3) and recently refined (4) to reproduce a microenvironment for marrow structural development and for suitable for hematopoiesis. P. falciparum transgenic lines producing fluorescent gametocytes, have been used in the BMHM model to investigate gametocyte-BM interactions obtaining preliminary results on parasite (i) vascular or extravascular distribution, (ii) sequestration timing, (iii) stage(s) involved.