Functional comparative investigation of the biology of Plasmodium spp. human bone marrow and peripheral blood

Malaria is a major public health problem worldwide. Plasmodium, the causative agent of malaria, reproduces asexually in erythrocytes, and there is also an enrichment of the parasite in hematopoietic niches, such as the bone marrow (BM) and spleen, due to the tropism of these parasites for immature reticulocytes that are present in this environment. Published data demonstrate that this enrichment in OM is important for the development of gametocytes and asexual forms, since recent data reinforce that peripheral parasitemia represents only a fraction of the total parasite biomass, while the majority accumulates and develops in the MO and in the spleen. However, the mechanisms involved in the cell tropism of this parasite are still not fully understood, and this fact represents an important bottleneck in understanding the biology and pathogenesis of the disease, and consequently in the diagnosis and treatment of malaria. In the present work, the hypothesis is that there are phenotypic and functional differences between populations of parasites that develop in hematopoietic niches, such as OM, and those found in peripheral blood (SP). To test this hypothesis, it is proposed to combine phenotypic and functional analyzes to investigate and compare the biology of parasites developing in erythrocytes from MO versus parasites developing in erythrocytes from SP. For this purpose, samples of BM and SP aspirates from volunteers from the Center for Hematology and Hemotherapy at UNICAMP recruited during the evaluation of remission for myelopathies and who do not present hematological alterations will be included. Reticulocyte populations from these tissues will be isolated and characterized by blood smear and flow cytometry. Subsequently, the cells will be used in functional assays, such as re-invasion assays, drug sensitivity, deformability (micropipette aspiration), cytoadhesion in endothelial cells and rosettes, as well as transcriptional analyzes, such as bulk RNA-seq and single-cell RNAseq. Finally, it is important to highlight that the project is being carried out in partnership with researchers from the Tropical Medicine Foundation in Manaus and the University of Glasgow, and that it is funded by FAPESP and the Medical Research Council of the United Kingdom. Furthermore, those collected were approved by the appropriate ethics committees, allowing the standardization of crucial tests for the execution of the proposal.

Project details

Basic Science

Jul 2023 — Jun 2024

Brazil