title: Reduced CD36-dependent tissue sequestration of Plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo.
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.
authors.affiliation: Leiden Malaria Research Group, Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
authors.forename: Jannik
authors.initials: J
authors.lastname: Fonager
authors.forename: Erica M
authors.initials: EM
authors.lastname: Pasini
authors.forename: Joanna A M
authors.initials: JA
authors.lastname: Braks
authors.forename: Onny
authors.initials: O
authors.lastname: Klop
authors.forename: Jai
authors.initials: J
authors.lastname: Ramesar
authors.forename: Edmond J
authors.initials: EJ
authors.lastname: Remarque
authors.forename: Irene O C M
authors.initials: IO
authors.lastname: Vroegrijk
authors.forename: Sjoerd G
authors.initials: SG
authors.lastname: van Duinen
authors.forename: Alan W
authors.initials: AW
authors.lastname: Thomas
authors.forename: Shahid M
authors.initials: SM
authors.lastname: Khan
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.forename: Clemens H M
authors.initials: CH
authors.lastname: Kocken
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Janse
authors.forename: Blandine M D
authors.initials: BM
authors.lastname: Franke-Fayard
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology*; D005260:Female; D008288:Malaria / Q000378:metabolism* / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D010962:Plasmodium berghei / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D021381:Protein Transport; D040901:Proteomics; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D052939:Schizonts / Q000378:metabolism; D013156:Splenectomy
chemical_list: D018955:CD36 Antigens; D015800:Protozoan Proteins