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Red Cell Biology & its Disorders
Altered parasite life-cycle processes characterize Babesia divergens infection in human sickle cell anemia
Ferrata Storti Foundation
Haematologica 2019 Volume 104(11):2189-2199
Jeny R. Cursino-Santos,1 Manpreet Singh,1 Eric Senaldi,2 Deepa Manwani,3 Karina Yazdanbakhsh4 and Cheryl A. Lobo1
1Department of Blood-Borne Parasites Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY; 2Medical Services New York Blood Center, New York, NY; 3Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY and 4Department of Complement Biology Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA
ABSTRACT
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 multi- tude of studies that have shown that the sickle trait has in fact been selected because of the protection it provides against a related Apicomplexan para- site, Plasmodium, that causes malaria. In this paper, we examine the impact of both the sickle cell anemia and sickle trait red blood cell (RBC) environ- ment on different aspects of the B. divergens life-cycle, and reveal that mul- tiple 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 wild- type RBC. The elucidation of these naturally occurring RBC resistance mechanisms is needed to shed light on host-parasite interaction, lend evo- lutionary insights into these related blood-borne parasites, and to provide new insights into the development of therapies against this disease.
Introduction
The human erythrocyte serves as the common host cell for two major Apicomplexan parasites, Plasmodium and Babesia. Both species invade, develop and egress from the red blood cell (RBC) following specific developmental programs that contribute to the majority of clinical symptoms associated with these infec- tions.1-3 Shielded within the host RBC, these intra-erythrocytic parasites differenti- ate and multiply while concealing their presence from the immune system. After filling the available intra-cellular space, the resultant parasite progeny egress as merozoites, and invade new RBC, carrying on the cycle of growth and proliferation. This cycle depends on intricate interactions between host RBC and parasite mole- cules. Thus, any perturbations to either the composition or arrangement of proteins on or within the host RBC can impact the parasite’s development and survival, and thus increase host resistance to parasite infection.
Much effort has been spent in determining the different means by which the human host can suppress this active parasite replication to limit the damage caused by the continuous destruction of the host RBC. One of the most commonly encountered mechanisms discovered is the genetic disorders that are found in the RBC.4 As the Plasmodium parasites have long co-existed with the human host, they have exerted extraordinary adaptive pressure on the human species.5 Consequently, in humans, multiple genetic polymorphisms have been selected for several hemo- globin disorders that provide intrinsic protection against severe malaria complica- tions and are convincingly supported by clinical data.6,7 Hemoglobin (Hb) is the oxy-
Correspondence:
CHERYL A. LOBO
CLobo@NYBloodcenter.org
Received: December 13, 2018. Accepted: March 20, 2019 Pre-published: March 28, 2019
doi:10.3324/haematol.2018.214304
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/11/2189
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haematologica | 2019; 104(11)
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