Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA.
Nat Commun. 2021 Mar 12;12(1):1629. doi: 10.1038/s41467-021-21886-x.
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.
宿主红细胞（RBC）的结构完整性对于疟原虫属在疟疾感染的致病血液阶段的传播至关重要。为了评估间日疟原虫感染网织红细胞的稳定性，我们开发了一种基于流式细胞术的测定法，用于测量特征性异质网织红细胞和间日疟原虫感染样本中的渗透稳定性。我们发现，在红细胞生成和网织红细胞成熟过程中，红细胞的渗透稳定性降低。在去核的 RBC 中，优先被间日疟原虫感染的年轻网织红细胞是最稳定的。然而，间日疟原虫感染会降低网织红细胞的稳定性，使其接近引起溶血性贫血的 RBC 疾病的水平，并且比恶性疟原虫使正常细胞不稳定的程度更大。最后，我们发现间日疟原虫的新通透性途径导致感染的网织红细胞渗透稳定性降低。这些结果揭示了间日疟原虫感染的网织红细胞的脆弱性，这可能会被操纵以允许体外培养和开发新的治疗方法。
