Altered parasite life-cycle processes characterize Babesia divergens infection in human sickle cell anemia
Altered parasite life-cycle processes characterize Babesia divergens infection in human sickle cell anemia
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DOI：
10.3324/haematol.2018.214304
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发表时间：
2019-10-30
期刊：
影响因子：
10.1
通讯作者：
Lobo, Cheryl A.
中科院分区：
文献类型：
--
作者：
Cursino-Santos, Jeny R.;Singh, Manpreet;Lobo, Cheryl A.
分歧巴贝虫是一种红细胞内寄生虫，在感染者中引起疟疾样症状。由于红细胞为寄生虫提供了生长和繁殖的基础结构，因此对细胞的任何扰动都会影响寄生虫的生存能力。支持这一点的是大量的研究，这些研究表明，镰刀状特征实际上是因为它提供了对相关的顶复门寄生虫的保护，疟原虫，导致疟疾。在本文中，我们研究了镰状细胞贫血和镰状性状红细胞（RBC）环境对B不同方面的影响。divergens生命周期，并揭示寄生虫生物过程的多个方面在突变型镰状贫血RBC中发生改变。这些过程包括寄生虫种群进展，可能由裂殖子感染性缺陷和/或从镰状细胞的排出缺陷引起，导致这些镰状细胞贫血细胞中寄生虫血症严重降低。相比之下，镰状性状RBC提供支持性环境，允许与野生型RBC的那些相当的体外感染率。需要阐明这些天然存在的RBC抗性机制，以阐明宿主-寄生虫相互作用，为这些相关的血源性寄生虫提供进化见解，并为开发针对这种疾病的疗法提供新的见解。
Babesia divergens is an intra-erythrocytic parasite that causes malaria-like symptoms in infected people. As the erythrocyte provides the parasite with the infra-structure to grow and multiply, any perturbation to the cell should impact parasite viability. Support for this comes from the multitude of studies that have shown that the sickle trait has in fact been selected because of the protection it provides against a related Apicomplexan parasite, Plasmodium, that causes malaria. In this paper, we examine the impact of both the sickle cell anemia and sickle trait red blood cell (RBC) environment on different aspects of the B. divergens life-cycle, and reveal that multiple aspects of parasite biological processes are altered in the mutant sickle anemia RBC. Such processes include parasite population progression, caused potentially by defective merozoite infectivity and/or defective egress from the sickle cell, resulting in severely lowered parasitemia in these cells with sickle cell anemia. In contrast, the sickle trait RBC provide a supportive environment permitting in vitro infection rates comparable to those of wildtype RBC. The elucidation of these naturally occurring RBC resistance mechanisms is needed to shed light on host-parasite interaction, lend evolutionary insights into these related blood-borne parasites, and to provide new insights into the development of therapies against this disease.