Journal article
Complement receptor 1 is the host erythrocyte receptor for Plasmodium falciparum PfRh4 invasion ligand
WH Tham, DW Wilson, S Lopaticki, CQ Schmidt, PB Tetteh-Quarcoo, PN Barlow, D Richard, JE Corbin, JG Beeson, AF Cowman
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2010
Abstract
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 weshow 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 Kd of 2.9 μM. PfRh4 binding is strongly correlated with the CR1 level on the erythrocyte surface. Parasite invasion via ..
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Funding Acknowledgements
We thank Dr. Henry C. Marsh (Celldex Therapeutics, Needham, MA) for providing sCR1, CR1 monoclonal antibodies 4D6 and 6B1, and comments on the manuscript. We thank Ronald Taylor (University of Virginia School of Medicine, Charlottesville, VA) and Thalachallour Mohanakumar (University of Virginia School of Medicine, Charlottesville, VA) for CR1 monoclonal antibodies 1B4, 3D9, 7G9, 9H3, and KuN241; the Australian Red Cross (Dr. Jenny Condon) for the blood samples; The Walter and Eliza Hall Institute's Monoclonal Facility (The Walter and Eliza Hall Institute of Medical Research, Melbourne) for antibody production; and Stuart Wyithe (Department of Physics, University of Melbourne, Melbourne) for statistical analysis. Infrastructure was supported by Victoria State Government Offer Information Statement and National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme grants. A.F.C. is a Howard Hughes International Scholar and an Australia Fellow of the National Health and Medical Research Council. J.G.B. is supported by a National Health and Medical Research Council Career Development award. This work was supported by the National Health and Medical Research Council, the Darwin Trust of Edinburgh (studentship to P.B.T-Q.), and the Wellcome Trust.