In vitro selection for adhesion of Plasmodium falciparum-infected erythrocytes to ABO antigens does not affect PfEMP1 and RIFIN expression

Sci Rep. 2020 Jul 30;10(1):12871. doi: 10.1038/s41598-020-69666-9.

Abstract

Plasmodium falciparum causes the most severe form of malaria in humans. The adhesion of the infected erythrocytes (IEs) to endothelial receptors (sequestration) and to uninfected erythrocytes (rosetting) are considered major elements in the pathogenesis of the disease. Both sequestration and rosetting appear to involve particular members of several IE variant surface antigens (VSAs) as ligands, interacting with multiple vascular host receptors, including the ABO blood group antigens. In this study, we subjected genetically distinct P. falciparum parasites to in vitro selection for increased IE adhesion to ABO antigens in the absence of potentially confounding receptors. The selection resulted in IEs that adhered stronger to pure ABO antigens, to erythrocytes, and to various human cell lines than their unselected counterparts. However, selection did not result in marked qualitative changes in transcript levels of the genes encoding the best-described VSA families, PfEMP1 and RIFIN. Rather, overall transcription of both gene families tended to decline following selection. Furthermore, selection-induced increases in the adhesion to ABO occurred in the absence of marked changes in immune IgG recognition of IE surface antigens, generally assumed to target mainly VSAs. Our study sheds new light on our understanding of the processes and molecules involved in IE sequestration and rosetting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ABO Blood-Group System / metabolism*
  • Animals
  • CHO Cells
  • Cricetulus
  • Erythrocytes* / metabolism
  • Erythrocytes* / parasitology
  • Gene Expression Regulation*
  • Humans
  • Malaria, Falciparum / metabolism*
  • Membrane Proteins / biosynthesis*
  • Plasmodium falciparum / metabolism*
  • Protozoan Proteins / biosynthesis*

Substances

  • ABO Blood-Group System
  • Membrane Proteins
  • Protozoan Proteins
  • RIFIN protein, Plasmodium falciparum
  • erythrocyte membrane protein 1, Plasmodium falciparum