chondroitin-sulfates and Malaria--Vivax

During

Topics: Animals; Antibodies, Protozoan; Antigens, Protozoan; Chondroitin Sulfates; Epitopes; Erythrocytes; Female; Malaria, Falciparum; Malaria, Vivax; Mice; Placenta; Plasmodium falciparum; Plasmodium vivax; Pregnancy; Protein Binding; Rats

Many pathogens evolve extensive genetic variation in virulence proteins as a strategy to evade host immunity. This poses a significant challenge for the host to develop broadly neutralizing antibodies. In

Topics: Animals; Antibodies, Protozoan; Antigens, Protozoan; Brazil; Cell Adhesion; Chondroitin Sulfates; Colombia; Cross Reactions; Epitope Mapping; Epitopes; Humans; Immunity, Heterologous; Malaria, Falciparum; Malaria, Vivax; Mice; Plasmodium falciparum; Plasmodium vivax; Protozoan Proteins; Receptors, Cell Surface; Uganda; Virulence Factors

In pregnancy, Plasmodium falciparum parasites express the surface antigen VAR2CSA, which mediates adherence of red blood cells to chondroitin sulfate A (CSA) in the placenta. VAR2CSA antibodies are generally acquired during infection in pregnancy and are associated with protection from placental malaria. We observed previously that men and children in Colombia also had antibodies to VAR2CSA, but the origin of these antibodies was unknown. Here, we tested whether infection with Plasmodium vivax is an alternative mechanism of acquisition of VAR2CSA antibodies.. We analyzed sera from nonpregnant Colombians and Brazilians exposed to P. vivax and monoclonal antibodies raised against P. vivax Duffy binding protein (PvDBP). Cross-reactivity to VAR2CSA was characterized by enzyme-linked immunosorbent assay, immunofluorescence assay, and flow cytometry, and antibodies were tested for inhibition of parasite binding to CSA.. Over 50% of individuals had antibodies that recognized VAR2CSA. Affinity-purified PvDBP human antibodies and a PvDBP monoclonal antibody recognized VAR2CSA, showing that PvDBP can give rise to cross-reactive antibodies. Importantly, the monoclonal antibody inhibited parasite binding to CSA, which is the primary in vitro correlate of protection from placental malaria.. These data suggest that PvDBP induces antibodies that functionally recognize VAR2CSA, revealing a novel mechanism of cross-species immune recognition to falciparum malaria.

Topics: Animals; Antibodies, Monoclonal; Antibodies, Protozoan; Antigens, Protozoan; Antigens, Surface; Child; Chondroitin Sulfates; Colombia; Cross Reactions; Erythrocytes; Eutheria; Female; Humans; Immunity; Malaria, Falciparum; Malaria, Vivax; Plasmodium falciparum; Plasmodium vivax; Pregnancy; Protozoan Proteins; Receptors, Cell Surface

Plasmodium vivax infections seldom kill directly but do cause indirect mortality by reducing birth weight and causing abortion. Cytoadherence and sequestration in the microvasculature are central to the pathogenesis of severe Plasmodium falciparum malaria, but the contribution of cytoadherence to pathology in other human malarias is less clear.. The adherence properties of P. vivax infected red blood cells (PvIRBC) were evaluated under static and flow conditions.. P. vivax isolates from 33 patients were studied. None adhered to immobilized CD36, ICAM-1, or thrombospondin, putative ligands for P. falciparum vascular cytoadherence, or umbilical vein endothelial cells, but all adhered to immobilized chondroitin sulphate A (CSA) and hyaluronic acid (HA), the receptors for adhesion of P. falciparum in the placenta. PvIRBC also adhered to fresh placental cells (N = 5). Pre-incubation with chondroitinase prevented PvIRBC adherence to CSA, and reduced binding to HA, whereas preincubation with hyaluronidase prevented adherence to HA, but did not reduce binding to CSA significantly. Pre-incubation of PvIRBC with soluble CSA and HA reduced binding to the immobilized receptors and prevented placental binding. PvIRBC adhesion was prevented by pre-incubation with trypsin, inhibited by heparin, and reduced by EGTA. Under laminar flow conditions the mean (SD) shear stress reducing maximum attachment by 50% was 0.06 (0.02) Pa but, having adhered, the PvIRBC could then resist detachment by stresses up to 5 Pa. At 37 °C adherence began approximately 16 hours after red cell invasion with maximal adherence at 30 hours. At 39 °C adherence began earlier and peaked at 24 hours.. Adherence of P. vivax-infected erythrocytes to glycosaminoglycans may contribute to the pathogenesis of vivax malaria and lead to intrauterine growth retardation.

Topics: Adult; Cell Adhesion; Chondroitin Sulfates; Egtazic Acid; Erythrocytes; Female; Glycosaminoglycans; Heparin; Humans; Hyaluronic Acid; Malaria, Vivax; Placenta; Plasmodium vivax; Pregnancy; Temperature; Trypsin