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

Fonager, Jannik; Pasini, Erica M.; Braks, Joanna A. M.; Klop, Onny; Ramesar, Jai; Remarque, Edmond J.; Vroegrijk, Irene O. C. M.; van Duinen, Sjoerd G.; Thomas, Alan W.; Khan, Shahid M.; Mann, Matthias; Kocken, Clemens H. M.; Janse, Chris J.; Franke-Fayard, Blandine M. D.

doi:10.1084/jem.20110762

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

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Mann, Matthias
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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引用

Fonager, J., Pasini, E. M., Braks, J. A. M., Klop, O., Ramesar, J., Remarque, E. J., Vroegrijk, I. O. C. M., van Duinen, S. G., Thomas, A. W., Khan, S. M., Mann, M., Kocken, C. H. M., Janse, C. J., & Franke-Fayard, B. M. D. (2012). Reduced CD36-dependent tissue sequestration of Plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo. JOURNAL OF EXPERIMENTAL MEDICINE, 209(1), 93-107. doi:10.1084/jem.20110762.

引用: https://hdl.handle.net/11858/00-001M-0000-000E-CADC-C

要旨

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 non-sequestering 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.