Complement receptor 1 is the host erythrocyte receptor for Plasmodium falciparum PfRh4 invasion ligand.
Plasmodium falciparum is responsible for the most severe form of malaria disease in humans, causing more than 1 million deaths each year. As an obligate intracellular parasite, P. falciparum's ability to invade erythrocytes is essential for its survival within the human host. P. falciparum invades erythrocytes using multiple host receptor-parasite ligand interactions known as invasion pathways. Here we show that CR1 is the host erythrocyte receptor for PfRh4, a major P. falciparum ligand essential for sialic acid-independent invasion. PfRh4 and CR1 interact directly, with a K(d) of 2.9 μM. PfRh4 binding is strongly correlated with the CR1 level on the erythrocyte surface. Parasite invasion via sialic acid-independent pathways is reduced in low-CR1 erythrocytes due to limited availability of this receptor on the surface. Furthermore, soluble CR1 can competitively block binding of PfRh4 to the erythrocyte surface and specifically inhibit sialic acid-independent parasite invasion. These results demonstrate that CR1 is an erythrocyte receptor used by the parasite ligand PfRh4 for P. falciparum invasion.
Tham
Wai-Hong
WH
The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Australia.
Wilson
Danny W
DW
Lopaticki
Sash
S
Schmidt
Christoph Q
CQ
Tetteh-Quarcoo
Patience B
PB
Barlow
Paul N
PN
Richard
Dave
D
Corbin
Jason E
JE
Beeson
James G
JG
Cowman
Alan F
AF
D000818:Animals; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism* / Q000469:parasitology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D011951:Receptors, Complement / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D008565:Membrane Proteins; D015800:Protozoan Proteins; C464927:RH4 protein, Plasmodium falciparum; D011951:Receptors, Complement; D011994:Recombinant Proteins; D019158:N-Acetylneuraminic Acid