Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

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}

Giardia intestinalis Incorporates Heme into Cytosolic Cytochrome b5.
J. Pyrih, K. Harant, E. Martincova, R. Sutak, E. Lesuisse, I. Hrdy, and J. Tachezy (2014)
Eukaryot. Cell 13, 231-239
   Abstract »    Full Text »    PDF »
Structural Basis for Inflammation-driven Shedding of CD163 Ectodomain and Tumor Necrosis Factor-{alpha} in Macrophages.
A. Etzerodt, M. R. Rasmussen, P. Svendsen, A. Chalaris, J. Schwarz, I. Galea, H. J. Moller, and S. K. Moestrup (2014)
J. Biol. Chem. 289, 778-788
   Abstract »    Full Text »    PDF »
Structure of the trypanosome haptoglobin-hemoglobin receptor and implications for nutrient uptake and innate immunity.
M. K. Higgins, O. Tkachenko, A. Brown, J. Reed, J. Raper, and M. Carrington (2013)
PNAS 110, 1905-1910
   Abstract »    Full Text »    PDF »
Aerobic kinetoplastid flagellate Phytomonas does not require heme for viability.
L. Koreny, R. Sobotka, J. Kovarova, A. Gnipova, P. Flegontov, A. Horvath, M. Obornik, F. J. Ayala, and J. Lukes (2012)
PNAS 109, 3808-3813
   Abstract »    Full Text »    PDF »
Rab28 function in trypanosomes: interactions with retromer and ESCRT pathways.
J. H. Lumb, K. F. Leung, K. N. DuBois, and M. C. Field (2011)
J. Cell Sci. 124, 3771-3783
   Abstract »    Full Text »    PDF »
Independent Analysis of the Flagellum Surface and Matrix Proteomes Provides Insight into Flagellum Signaling in Mammalian-infectious Trypanosoma brucei.
M. Oberholzer, G. Langousis, H. T. Nguyen, E. A. Saada, M. M. Shimogawa, Z. O. Jonsson, S. M. Nguyen, J. A. Wohlschlegel, and K. L. Hill (2011)
Mol. Cell. Proteomics 10, M111.010538
   Abstract »    Full Text »    PDF »
Endosomal Localization of the Serum Resistance-Associated Protein in African Trypanosomes Confers Human Infectivity.
N. A. Stephens and S. L. Hajduk (2011)
Eukaryot. Cell 10, 1023-1033
   Abstract »    Full Text »    PDF »
Cell Biology of the Trypanosome Genome.
J.-P. Daniels, K. Gull, and B. Wickstead (2010)
Microbiol. Mol. Biol. Rev. 74, 552-569
   Abstract »    Full Text »    PDF »
Tumor necrosis factor {alpha}-converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163.
A. Etzerodt, M. B. Maniecki, K. Moller, H. J. Moller, and S. K. Moestrup (2010)
J. Leukoc. Biol. 88, 1201-1205
   Abstract »    Full Text »    PDF »
Mechanism of Trypanosoma brucei gambiense (group 1) resistance to human trypanosome lytic factor.
R. Kieft, P. Capewell, C. M. R. Turner, N. J. Veitch, A. MacLeod, and S. Hajduk (2010)
PNAS 107, 16137-16141
   Abstract »    Full Text »    PDF »
Cellular and Molecular Remodeling of the Endocytic Pathway during Differentiation of Trypanosoma brucei Bloodstream Forms.
B. Vanhollebeke, P. Uzureau, D. Monteyne, D. Perez-Morga, and E. Pays (2010)
Eukaryot. Cell 9, 1272-1282
   Abstract »    Full Text »    PDF »
Crystal Structures of Trypanosoma brucei Sterol 14{alpha}-Demethylase and Implications for Selective Treatment of Human Infections.
G. I. Lepesheva, H.-W. Park, T. Y. Hargrove, B. Vanhollebeke, Z. Wawrzak, J. M. Harp, M. Sundaramoorthy, W. D. Nes, E. Pays, M. Chaudhuri, et al. (2010)
J. Biol. Chem. 285, 1773-1780
   Abstract »    Full Text »    PDF »
Hydrodynamic gene delivery of baboon trypanosome lytic factor eliminates both animal and human-infective African trypanosomes.
R. Thomson, P. Molina-Portela, H. Mott, M. Carrington, and J. Raper (2009)
PNAS 106, 19509-19514
   Abstract »    Full Text »    PDF »
Membrane domains and flagellar pocket boundaries are influenced by the cytoskeleton in African trypanosomes.
C. Gadelha, S. Rothery, M. Morphew, J. R. McIntosh, N. J. Severs, and K. Gull (2009)
PNAS 106, 17425-17430
   Abstract »    Full Text »    PDF »
Receptor targeting of hemoglobin mediated by the haptoglobins: roles beyond heme scavenging.
M. J. Nielsen and S. K. Moestrup (2009)
Blood 114, 764-771
   Abstract »    Full Text »    PDF »
Membrane Permeabilization by Trypanosome Lytic Factor, a Cytolytic Human High Density Lipoprotein.
J. M. Harrington, S. Howell, and S. L. Hajduk (2009)
J. Biol. Chem. 284, 13505-13512
   Abstract »    Full Text »    PDF »
The apolipoprotein L family of programmed cell death and immunity genes rapidly evolved in primates at discrete sites of host-pathogen interactions.
E. E. Smith and H. S. Malik (2009)
Genome Res. 19, 850-858
   Abstract »    Full Text »    PDF »
Three-dimensional cellular architecture of the flagellar pocket and associated cytoskeleton in trypanosomes revealed by electron microscope tomography.
S. Lacomble, S. Vaughan, C. Gadelha, M. K. Morphew, M. K. Shaw, J. R. McIntosh, and K. Gull (2009)
J. Cell Sci. 122, 1081-1090
   Abstract »    Full Text »    PDF »
Distinct roles of apolipoprotein components within the trypanosome lytic factor complex revealed in a novel transgenic mouse model.
M. P. Molina-Portela, M. Samanovic, and J. Raper (2008)
J. Exp. Med. 205, 1721-1728
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882