Reduced CD36-dependent tissue sequestration of Plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo

J Exp Med. 2012 Jan 16;209(1):93-107. doi: 10.1084/jem.20110762. Epub 2011 Dec 19.


Adherence of parasite-infected red blood cells (irbc) to the vascular endothelium of organs plays a key role in the pathogenesis of Plasmodium falciparum malaria. The prevailing hypothesis of why irbc adhere and sequester in tissues is that this acts as a mechanism of avoiding spleen-mediated clearance. Irbc of the rodent parasite Plasmodium berghei ANKA sequester in a fashion analogous to P. falciparum by adhering to the host receptor CD36. To experimentally determine the significance of sequestration for parasite growth, we generated a mutant P. berghei ANKA parasite with a reduced CD36-mediated adherence. Although the cognate parasite ligand binding to CD36 is unknown, we show that nonsequestering parasites have reduced growth and we provide evidence that in addition to avoiding spleen removal, other factors related to CD36-mediated sequestration are beneficial for parasite growth. These results reveal for the first time the importance of sequestration to a malaria infection, with implications for the development of strategies aimed at reducing pathology by inhibiting tissue sequestration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD36 Antigens / genetics
  • CD36 Antigens / metabolism*
  • Cell Adhesion / genetics
  • Cell Cycle / genetics
  • Erythrocytes / metabolism*
  • Erythrocytes / parasitology*
  • Female
  • Malaria / metabolism*
  • Malaria / parasitology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation
  • Plasmodium berghei / genetics
  • Plasmodium berghei / growth & development
  • Plasmodium berghei / metabolism*
  • Protein Transport
  • Proteomics
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • Rats
  • Rats, Wistar
  • Schizonts / metabolism
  • Splenectomy


  • CD36 Antigens
  • Protozoan Proteins