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Science 320 (5876): 677-681

Copyright © 2008 by the American Association for the Advancement of Science

A Haptoglobin-Hemoglobin Receptor Conveys Innate Immunity to Trypanosoma brucei in Humans

Benoit Vanhollebeke,1 Géraldine De Muylder,1 Marianne J. Nielsen,2 Annette Pays,1 Patricia Tebabi,1 Marc Dieu,3 Martine Raes,3 Soren K. Moestrup,2 Etienne Pays1*

Abstract: The protozoan parasite Trypanosoma brucei is lysed by apolipoprotein L-I, a component of human high-density lipoprotein (HDL) particles that are also characterized by the presence of haptoglobin-related protein. We report that this process is mediated by a parasite glycoprotein receptor, which binds the haptoglobin-hemoglobin complex with high affinity for the uptake and incorporation of heme into intracellular hemoproteins. In mice, this receptor was required for optimal parasite growth and the resistance of parasites to the oxidative burst by host macrophages. In humans, the trypanosome receptor also recognized the complex between hemoglobin and haptoglobin-related protein, which explains its ability to capture trypanolytic HDLs. Thus, in humans the presence of haptoglobin-related protein has diverted the function of the trypanosome haptoglobin-hemoglobin receptor to elicit innate host immunity against the parasite.

1 Laboratory of Molecular Parasitology, Institute for Molecular Biology and Medicine, Université Libre de Bruxelles, 12 rue des Profs Jeener et Brachet, B6041 Gosselies, Belgium.
2 Department of Medical Biochemistry, University of Aarhus, DK-8000 Aarhus, Denmark.
3 Unit of Cellular Biochemistry and Biology, University of Namur, B5000 Namur, Belgium.

* To whom correspondence should be addressed. E-mail: epays{at}ulb.ac.be


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