Hematopoietic niches promote initiation of malaria transmission and evasion of chemotherapy

[摘要] The transmission of the malaria parasite (Plasmodium spp) is effected by a small proportion of the population that commit to sexual development forming either male or female gametocytes. Currently front-line anti-malarials are developed to treat the asexual life stage parasitising mature erythrocytes. While circulating mature erythrocytes form a relatively homogenous population, it has been recently established that Plasmodium spp can colonise progenitor cells in the erythroid lineage. I hypothesised that these tissue-resident erythroid precursors may form a niche for preferential development of gametocytes, and therefore developed a quantitative approach to enumerate Plasmodium-infected erythropoietic intermediate cells in haematopoietic tissues. We demonstrate that within erythropoietic tissues, early reticulocytes preferentially drive commitment to gametocytogenesis, with the splenic niche contributing the quantifiable majority of gametocytes. Furthermore, this same erythropoetic niche offers the parasite protection against antimalarial drug treatment and, as such, may serve as origins of recrudescent infection and continuing transmission. My data therefore demonstrate that host cell phenotype and location play an active role in determining the developmental fate of malaria parasites and furthermore suggests a mechanism for the persistence of malaria parasites.

[发布机构] University:University of Glasgow;Department:Institute of Infection Immunity and Inflammation

[关键词] Plasmodium.