Abstract
The extensive redundancy in the use of invasion ligands by Plasmodium falciparum, and its unique ability to switch between invasion pathways have hampered vaccine development. P. falciparum strains Dd2 and W2mef have been shown to change from sialic acid (SA)-dependent to SA-independent phenotypes when selected on neuraminidase-treated erythrocytes. Following an observation of increasing ability of Dd2 to invade neuraminidase-treated cells when cultured for several weeks, we systematically investigated this phenomenon by comparing invasion phenotypes of Dd2, W2mef and 3D7 strains of P. falciparum that were cultured with gentle shaking (Suspended) or under static (Static) conditions. While Static Dd2 and W2mef remained SA-dependent for the entire duration of the investigation, Suspended parasites spontaneously and progressively switched to SA-independent phenotype from week 2 onwards. Furthermore, returning Suspended cultures to Static conditions led to a gradual reversal to SA-dependent phenotype. The switch to SA-independent phenotype was accompanied by upregulation of the key invasion ligand, reticulocyte-binding homologue 4 (RH4), and the increased invasion was inhibited by antibodies to the RH4 receptor, CR1. Our data demonstrates a novel mechanism for inducing the switching of invasion pathways in P. falciparum parasites and may provide clues for understanding the mechanisms involved.
Highlights
As an obligate intracellular parasite, Plasmodium falciparum actively invades and establishes successful infection in human erythrocytes, making erythrocyte invasion an attractive target for malaria vaccine development[1]
Our results provide a new twist in the complexity of P. falciparum invasion mechanisms, and has interesting implications on the physiological relevance of methods used for parasite cultivation in vitro and the study of invasion phenotypes in culture-adapted clinical isolates
Both parasite strains are capable of switching invasion phenotype when continuously selected on neuraminidase (Nm)-treated erythrocytes[28,30]
Summary
As an obligate intracellular parasite, Plasmodium falciparum actively invades and establishes successful infection in human erythrocytes, making erythrocyte invasion an attractive target for malaria vaccine development[1]. These data demonstrate that if cultured continuously with shaking, Dd2 and W2mef parasite strains could spontaneously switch to SA-independent invasion phenotype, while maintaining their genetic identity.
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