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Reduced CD36-dependent tissue sequestration of Plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2012 Jan 16; Vol. 209 (1), pp. 93-107. Date of Electronic Publication: 2011 Dec 19. - Publication Year :
- 2012
-
Abstract
- 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.
- Subjects :
- Animals
CD36 Antigens genetics
Cell Adhesion genetics
Cell Cycle genetics
Female
Mice
Mice, Inbred C57BL
Mice, Knockout
Mutation
Plasmodium berghei genetics
Plasmodium berghei growth & development
Protein Transport
Proteomics
Protozoan Proteins genetics
Protozoan Proteins metabolism
Rats
Rats, Wistar
Schizonts metabolism
Splenectomy
CD36 Antigens metabolism
Erythrocytes metabolism
Erythrocytes parasitology
Malaria metabolism
Malaria parasitology
Plasmodium berghei metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 209
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 22184632
- Full Text :
- https://doi.org/10.1084/jem.20110762