title: Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration.
abstract: Sequestration of malaria-parasite-infected erythrocytes in the microvasculature of organs is thought to be a significant cause of pathology. Cerebral malaria (CM) is a major complication of Plasmodium falciparum infections, and PfEMP1-mediated sequestration of infected red blood cells has been considered to be the major feature leading to CM-related pathology. We report a system for the real-time in vivo imaging of sequestration using transgenic luciferase-expressing parasites of the rodent malaria parasite Plasmodium berghei. These studies revealed that: (i) as expected, lung tissue is a major site, but, unexpectedly, adipose tissue contributes significantly to sequestration, and (ii) the class II scavenger-receptor CD36 to which PfEMP1 can bind is also the major receptor for P. berghei sequestration, indicating a role for alternative parasite ligands, because orthologues of PfEMP1 are absent from rodent malaria parasites, and, importantly, (iii) cerebral complications still develop in the absence of CD36-mediated sequestration, dissociating parasite sequestration from CM-associated pathology. Real-time in vivo imaging of parasitic processes may be used to evaluate the molecular basis of pathology and develop strategies to prevent pathology.
authors.affiliation: Department of Parasitology, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
authors.forename: Blandine
authors.initials: B
authors.lastname: Franke-Fayard
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Janse
authors.forename: Margarida
authors.initials: M
authors.lastname: Cunha-Rodrigues
authors.forename: Jai
authors.initials: J
authors.lastname: Ramesar
authors.forename: Philippe
authors.initials: P
authors.lastname: Büscher
authors.forename: Ivo
authors.initials: I
authors.lastname: Que
authors.forename: Clemens
authors.initials: C
authors.lastname: Löwik
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Voshol
authors.forename: Marion A M
authors.initials: MA
authors.lastname: den Boer
authors.forename: Sjoerd G
authors.initials: SG
authors.lastname: van Duinen
authors.forename: Maria
authors.initials: M
authors.lastname: Febbraio
authors.forename: Maria M
authors.initials: MM
authors.lastname: Mota
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Waters
mesh_terms: D000273:Adipose Tissue / Q000469:parasitology / Q000473:pathology; D000818:Animals; D001921:Brain / Q000469:parasitology / Q000473:pathology; D018955:CD36 Antigens / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology*; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D008156:Luciferases / Q000378:metabolism; D008168:Lung / Q000469:parasitology / Q000473:pathology; D016779:Malaria, Cerebral / Q000473:pathology* / Q000503:physiopathology*; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D010962:Plasmodium berghei / Q000235:genetics* / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism; D013997:Time Factors
chemical_list: D018955:CD36 Antigens; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D049452:Green Fluorescent Proteins; D008156:Luciferases