Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria.
Haemoglobin C, which carries a glutamate-to-lysine mutation in the beta-globin chain, protects West African children against Plasmodium falciparum malaria. Mechanisms of protection are not established for the heterozygous (haemoglobin AC) or homozygous (haemoglobin CC) states. Here we report a marked effect of haemoglobin C on the cell-surface properties of P. falciparum-infected erythrocytes involved in pathogenesis. Relative to parasite-infected normal erythrocytes (haemoglobin AA), parasitized AC and CC erythrocytes show reduced adhesion to endothelial monolayers expressing CD36 and intercellular adhesion molecule-1 (ICAM-1). They also show impaired rosetting interactions with non-parasitized erythrocytes, and reduced agglutination in the presence of pooled sera from malaria-immune adults. Abnormal cell-surface display of the main variable cytoadherence ligand, PfEMP-1 (P. falciparum erythrocyte membrane protein-1), correlates with these findings. The abnormalities in PfEMP-1 display are associated with markers of erythrocyte senescence, and are greater in CC than in AC erythrocytes. Haemoglobin C might protect against malaria by reducing PfEMP-1-mediated adherence of parasitized erythrocytes, thereby mitigating the effects of their sequestration in the microvasculature.
Laboratory of Malaria and Vector Research, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Rick M
RM
Fairhurst
Dror I
DI
Baruch
Nathaniel J
NJ
Brittain
Graciela R
GR
Ostera
John S
JS
Wallach
Holly L
HL
Hoang
Karen
K
Hayton
Aldiouma
A
Guindo
Morris O
MO
Makobongo
Owen M
OM
Schwartz
Anatole
A
Tounkara
Ogobara K
OK
Doumbo
Dapa A
DA
Diallo
Hisashi
H
Fujioka
May
M
Ho
Thomas E
TE
Wellems
D000818:Animals; D000906:Antibodies / Q000276:immunology; D018955:CD36 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D004903:Erythrocyte Aggregation; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology* / Q000473:pathology; D005434:Flow Cytometry; D006420:Hemeproteins / Q000378:metabolism; D006444:Hemoglobin C / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008288:Malaria / Q000097:blood* / Q000469:parasitology / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000472:pathogenicity / Q000502:physiology*; D015800:Protozoan Proteins / Q000378:metabolism*
D000906:Antibodies; D018955:CD36 Antigens; D006420:Hemeproteins; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; C001332:hemichrome; D018799:Intercellular Adhesion Molecule-1; D006444:Hemoglobin C