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.
Fairhurst
Rick M
RM
Laboratory of Malaria and Vector Research, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Baruch
Dror I
DI
Brittain
Nathaniel J
NJ
Ostera
Graciela R
GR
Wallach
John S
JS
Hoang
Holly L
HL
Hayton
Karen
K
Guindo
Aldiouma
A
Makobongo
Morris O
MO
Schwartz
Owen M
OM
Tounkara
Anatole
A
Doumbo
Ogobara K
OK
Diallo
Dapa A
DA
Fujioka
Hisashi
H
Ho
May
M
Wellems
Thomas E
TE
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