Complement and Antibody-Mediated Enhancement of Erythrocyte Invasion by Plasmodium Falciparum
Technical Report,01 Aug 2014,31 Aug 2015
The Pennsylvania State University Hershey United States
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Plasmodium falciparum malaria kills hundreds of thousands of people every year. A vaccine that blocks red blood cell RBC invasion has been an elusive goal. Although anti-merozoite antibodies block invasion in vitro, there is no efficacy in vivo. Since merozoites are able to utilize the complement receptor 1 CR1 on RBCs to invade we reasoned that complement activation could enhance invasion. To test this hypothesis we studied the role of complement in RBC invasion in vitro and parasite growth in an animal model. Fresh serum enhanced RBC invasion relative to heat-inactivated serum HIS. Anti-merozoites monoclonal mAb5.2, directed against MSP119, induced invasion enhancement that was inhibited by HIS, the C3 inhibitor compstatin, and soluble CR1 sCR1. Antibody and complement-mediated invasion led to aggregation and colocalization of CR1, C3, and lipids on the RBC surface at the point of merozoite contact. Total IgG from MSP142 vaccines enhanced invasion in a complement-dependent manner. Finally, total anti-P. berghei IgG enhanced parasite growth in mice and C3-deficient mice showed decreased parasite growth relative to wild type mice. Our results demonstrate that merozoites are able to use complement to invade RBCs and, thus, hijack the complement system and evade the host immune response.