Abstract
Naturally acquired antibodies to proteins expressed on the Plasmodium falciparum parasitized red blood cell (pRBC) surface steer the course of a malaria infection by reducing sequestration and stimulating phagocytosis of pRBC. Here we have studied a selection of proteins representing three different parasite gene families employing a well-characterized parasite with a severe malaria phenotype (FCR3S1.2). The presence of naturally acquired antibodies, impact on rosetting rate, surface reactivity and opsonization for phagocytosis in relation to different blood groups of the ABO system were assessed in a set of sera from children with mild or complicated malaria from an endemic area. We show that the naturally acquired immune responses, developed during malaria natural infection, have limited access to the pRBCs inside a blood group A rosette. The data also indicate that SURFIN4.2 may have a function at the pRBC surface, particularly during rosette formation, this role however needs to be further validated. Our results also indicate epitopes differentially recognized by rosette-disrupting antibodies on a peptide array. Antibodies towards parasite-derived proteins such as PfEMP1, RIFIN and SURFIN in combination with host factors, essentially the ABO blood group of a malaria patient, are suggested to determine the outcome of a malaria infection.
Highlights
Despite ongoing eradication efforts and a marked decrease in the number of malaria cases over the last 15 years, malaria is still endemic in 91 countries with an estimated of 212 million malaria cases and 429000 deaths during 2016, with P. falciparum being the most prevalent parasite in the African continent and the main responsible for the deadly cases[1]
The rosetting phenotype varies among isolates and has been clearly associated to the progression of infected individuals into severe disease[3,4,5,6], certain human phenotypes including the ABO blood group[7,8,9] as well as the presence of rosette disrupting and opsonizing antibodies are considered a protective factor against severe disease development[42,43]
Sera from children naturally exposed to malaria and presenting with an episode of mild or complicated malaria were tested for their ability to recognize the parasitized red blood cell (pRBC) surface of group O or group A grown parasites and more importantly for their ability to disrupt rosettes and opsonize for phagocytosis
Summary
Despite ongoing eradication efforts and a marked decrease in the number of malaria cases over the last 15 years, malaria is still endemic in 91 countries with an estimated of 212 million malaria cases and 429000 deaths during 2016, with P. falciparum being the most prevalent parasite in the African continent and the main responsible for the deadly cases[1]. Malaria clinical symptoms occur when parasites invade and multiply inside the human red blood cells (RBCs) where they transport proteins to the RBC cytoplasm and plasma membrane. These proteins confer adhesive characteristics to the parasitized RBCs (pRBCs) allowing their sequestration in the microvasculature, a hallmark process in the pathogenesis of severe malaria[2]. Rosettes formed in the presence of group A RBCs have been suggested as a mechanism to evade immune recognition by impairing antibody accessibility to parasite proteins on the surface of the pRBCs18. Specific epitopes on the three proteins were identified as possible candidates involved in the rosetting phenotype These parameters were contrasted between parasites grown in group O or group A RBCs
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