4.8 Article

Plasmodium vivax infection compromises reticulocyte stability

Journal

NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -

Publisher

NATURE RESEARCH
DOI: 10.1038/s41467-021-21886-x

Keywords

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Funding

  1. U.S. NIH/NHLBI [F32 HL136173]
  2. NIH [R01 AI140751, R01 HL139337]
  3. NIH/NIAID MESA-ICEMR Program [U19 AI89688]
  4. Canadian Institutes of Health Research Postdoctoral Fellowship
  5. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
  6. Ministry of Health of Brazil
  7. CNPq [404067/2012-3]

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During Plasmodium intra-erythrocytic development, parasites compromise the structural integrity of host red-blood cells. Researchers found that P. vivax infection destabilizes host reticulocytes, which are less stable than normocytes infected with P. falciparum.
The structural integrity of the host red blood cell (RBC) is crucial for propagation of Plasmodium spp. during the disease-causing blood stage of malaria infection. To assess the stability of Plasmodium vivax-infected reticulocytes, we developed a flow cytometry-based assay to measure osmotic stability within characteristically heterogeneous reticulocyte and P. vivax-infected samples. We find that erythroid osmotic stability decreases during erythropoiesis and reticulocyte maturation. Of enucleated RBCs, young reticulocytes which are preferentially infected by P. vivax, are the most osmotically stable. P. vivax infection however decreases reticulocyte stability to levels close to those of RBC disorders that cause hemolytic anemia, and to a significantly greater degree than P. falciparum destabilizes normocytes. Finally, we find that P. vivax new permeability pathways contribute to the decreased osmotic stability of infected-reticulocytes. These results reveal a vulnerability of P. vivax-infected reticulocytes that could be manipulated to allow in vitro culture and develop novel therapeutics. During Plasmodium intra-erythrocytic developmental, parasites compromise the structural integrity of host red-blood cells. Here, Clark et al. develop a flow cytometric osmotic stability assay to show that P. vivax infection destabilizes host reticulocytes, which are less stable than P. falciparum-infected normocytes.

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