School of Biochemistry, University of Bristol, Bristol, United Kingdom.
Front Cell Infect Microbiol. 2022 Nov 14;12:1039520. doi: 10.3389/fcimb.2022.1039520. eCollection 2022.
Parasites of the genus that cause malaria survive within humans by invasion of, and proliferation within, the most abundant cell type in the body, the red blood cell. As obligate, intracellular parasites, interactions between parasite and host red blood cell components are crucial to multiple aspects of the blood stage malaria parasite lifecycle. The requirement for, and involvement of, an array of red blood cell proteins in parasite invasion and intracellular development is well established. Nevertheless, detailed mechanistic understanding of host cell protein contributions to these processes are hampered by the genetic intractability of the anucleate red blood cell. The advent of stem cell technology and more specifically development of methods that recapitulate the process of red blood cell development known as erythropoiesis has enabled the generation of erythroid cell stages previously inaccessible in large numbers for malaria studies. What is more, the capacity for genetic manipulation of nucleated erythroid precursors that can be differentiated to generate modified red blood cells has opened new horizons for malaria research. This review summarises current methodologies that harness erythroid differentiation of stem cells for generation of cells that are susceptible to malaria parasite invasion; discusses existing and emerging approaches to generate novel red blood cell phenotypes and explores the exciting potential of derived red blood cells for improved understanding the broad role of host red blood cell proteins in malaria pathogenesis.
疟原虫属寄生虫通过入侵和在体内最丰富的细胞类型——红细胞内增殖而在人体内存活。作为专性内寄生寄生虫，寄生虫和宿主红细胞成分之间的相互作用对疟原虫生命周期的多个方面至关重要。红细胞蛋白在寄生虫入侵和细胞内发育中的作用和参与已得到充分证实。然而，由于无核红细胞的遗传复杂性，对这些过程中宿主细胞蛋白贡献的详细机制理解受到阻碍。干细胞技术的出现，特别是能够重现红细胞发育过程（称为红细胞生成）的方法的发展，使得以前无法大量获得用于疟疾研究的红细胞阶段得以产生。更重要的是，对可分化为产生改良红细胞的有核红细胞前体进行遗传操作的能力为疟疾研究开辟了新的前景。这篇综述总结了当前利用干细胞的红细胞分化来产生易受疟原虫入侵的细胞的方法；讨论了生成新型红细胞表型的现有和新兴方法，并探讨了衍生红细胞在更好地理解宿主红细胞蛋白在疟疾发病机制中的广泛作用方面的令人兴奋的潜力。
