New insights into the altered adhesive and mechanical properties of red blood cells parasitized by Babesia bovis

Abstract

SummarySequestration of parasite-infected red blood cells (RBCs) in the microvasculature is an important pathological feature of both bovine babesiosis caused by Babesia bovis and human malaria caused by Plasmodium falciparum. Surprisingly, when compared with malaria, the cellular and molecular mechanisms that underlie this abnormal circulatory behaviour for RBCs infected with B. bovis have been relatively ignored. Here, we present some novel insights into the adhesive and mechanical changes that occur in B. bovis-infected bovine RBCs and compare them with the alterations that occur in human RBCs infected with P. falciparum. After infection with B. bovis, bovine RBCs become rigid and adhere to vascular endothelial cells under conditions of physiologically relevant flow. These alterations are accompanied by the appearance of ridge-like structures on the RBC surface that are analogous, but morphologically and biochemically different, to the knob-like structures on the surface of human RBCs infected with P. falciparum. Importantly, albeit for a limited number of parasite lines examined here, the extent of these cellular and rheological changes appear to be related to parasite virulence. Future investigations to identify the precise molecular composition of ridges and the proteins that mediate adhesion will provide important insight into the pathogenesis of both babesiosis and malaria.

Red cell exchange transfusion for babesiosis in Rhode Island

“…Red cell sequestration, the adhesion of parasite infected erythrocytes to endothelial cells leading to a restriction of blood flow to the microcirculation tissue causing deoxygenation and endothelial destruction, has been described in Plasmodium falciparum infection [32,40,45]. While bovine studies have demonstrated red cell sequestration during babesial infections with Babesia bovis, red cell sequestration has not been demonstrated in human studies [46,50,51] If red cell sequestration does occur in human babesiosis, its contribution to end organ failure is likely limited. The beneficial role of RCE or WBE in this condition is therefore still unclear but removal of the rigid uninfected cells could decrease obstruction in the microcirculation [40].…”

The avian malaria parasite Plasmodium gallinaceum causes marked structural changes on the surface of its host erythrocyte

“…It was recently reported that bovine erythrocytes infected with the apicomplexan parasite Babesia bovis show 200 nm-long ridge-like protrusions on their surface (Hutchings et al, 2007). A proposed hypothesis is that these structures represent parasite-derived proteins associating and aligning themselves along the length of spectrin molecules.…”

Preliminary Evaluation of the Br EMA1 Gene as a Tool for Associating Babesia rossi Genotypes and Clinical Manifestation of Canine Babesiosis

“…Furthermore, there is no evidence related to the involvement of BrEMA1 in sequestration. It has been demonstrated, though, that both adhesive and mechanical properties of P. falciparum-or B. bovis-infected red blood cells play a pivotal role in their ability to sequester parasites and, consequently, in the virulence of these parasites (6,8). If virulence is indeed directly related to cytoadhesion, as suggested by the B. bovis model (1, 2), then more work should be undertaken to correlate the relationship between the virulent BrEMA1 genotypes and cytoadhesion or to identify auxiliary genes that may play a role in this phenomenon.…”