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

American Association for the Advancement of Science (AAAS) - Tập 320 Số 5876 - Trang 677-681 - 2008
Benoît Vanhollebeke1,2,3, Géraldine De Muylder1,2,3, Marianne Jensby Nielsen1,2,3, Annette Pays1,2,3, Patricia Tebabi1,2,3, Marc Dieu1,2,3, Martine Raes1,2,3, Søren K. Moestrup1,2,3, Étienne Pays1,2,3
1Department of Medical Biochemistry, University of Aarhus, DK-8000 Aarhus, Denmark.
2Laboratory of Molecular Parasitology, Institute for Molecular Biology and Medicine, Université Libre de Bruxelles, 12 rue des Profs Jeener et Brachet, B6041 Gosselies, Belgium.
3Unit of Cellular Biochemistry and Biology, University of Namur, B5000 Namur, Belgium.

Tóm tắt

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.

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We thank C. Jacobsen L. Hederstedt M. Boutry A. Beschin A. Jacquet S. Denanglaire A. M. Bundsgaard E. Dupont and D. Nolan for advice and help and P. Brouckaert and E. Tolosano for iNOS –/– and Hp –/– mice respectively. This work was supported by the Belgian National Fund for Scientific Research the J. Brachet Fund the Danish Medical Research Council and the Interuniversity Attraction Poles Programme—Belgian Science Policy. B.V. and G.D. are research fellows at the Fonds National de la Recherche Scientifique and Fonds de la Recherche pour l'Industrie et l'Agriculture respectively.

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American Association for the Advancement of Science (AAAS)

Tập 320 Số 5876

677-681

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