On the Cytoadhesion of Plasmodium vivax-Infected Erythrocytes

Background. Plasmodium falciparum and Plasmodium vivax are responsible for most of the global burden of malaria. Although the accentuated pathogenicity of P. falciparum occurs because of sequestration of the mature erythrocytic forms in the microvasculature, this phenomenon has not yet been noted in P. vivax. The increasing number of severe manifestations of P. vivax infections, similar to those observed for severe falciparum malaria, suggests that key pathogenic mechanisms (eg, cytoadherence) might be shared by the 2 parasites. Methods. Mature P. vivax-infected erythrocytes (Pv-iEs) were isolated from blood samples collected from 34 infected patients. Pv-iEs enriched on Percoll gradients were used in cytoadhesion assays with human lung endothelial cells, Saimiri brain endothelial cells, and placental cryosections. Results. Pv-iEs were able to cytoadhere under static and flow conditions to cells expressing endothelial receptors known to mediate the cytoadhesion of P. falciparum. Although Pv-iE cytoadhesion levels were 10-fold lower than those observed for P. falciparum-infected erythrocytes, the strength of the interaction was similar. Cytoadhesion of Pv-iEs was in part mediated by VIR proteins, encoded by P. vivax variant genes (vir), given that specific antisera inhibited the Pv-iE-endothelial cell interaction. Conclusions. These observations prompt a modification of the current paradigms of the pathogenesis of malaria and clear the way to investigate the pathophysiology of P. vivax infections.

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[04/00638-6]

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[05/60569-0]

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[09/52013-3]

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)

Instituto Nacional de Tecnologia em Vacinas (CNPq-FAPEMIG) (INCT)

Doencas Negligenciadas[576128/2008-2]

CNPq

CAPES Coordenacao de Aperfeicoamento de Pessoal de Nivel

Agency for Science, Technology, and Research, Singapore

Institut National de la Sante et de la Recherche Medicale, France