Available on ORBi since
24 October 2013
Article (Scientific journals)
Mechanism of Trypanosoma brucei gambiense resistance to human serum.
Uzureau, Pierrick; Uzureau, Sophie; Lecordier, Laurence et al.
2013In Nature, 501 (7467), p. 430-4
Peer Reviewed verified by ORBi


Full Text
Author postprint (1.08 MB)

All documents in ORBi are protected by a user license.

Send to


Abstract :
[en] The African parasite Trypanosoma brucei gambiense accounts for 97% of human sleeping sickness cases. T. b. gambiense resists the specific human innate immunity acting against several other tsetse-fly-transmitted trypanosome species such as T. b. brucei, the causative agent of nagana disease in cattle. Human immunity to some African trypanosomes is due to two serum complexes designated trypanolytic factors (TLF-1 and -2), which both contain haptoglobin-related protein (HPR) and apolipoprotein LI (APOL1). Whereas HPR association with haemoglobin (Hb) allows TLF-1 binding and uptake via the trypanosome receptor TbHpHbR (ref. 5), TLF-2 enters trypanosomes independently of TbHpHbR (refs 4, 5). APOL1 kills trypanosomes after insertion into endosomal/lysosomal membranes. Here we report that T. b. gambiense resists TLFs via a hydrophobic beta-sheet of the T. b. gambiense-specific glycoprotein (TgsGP), which prevents APOL1 toxicity and induces stiffening of membranes upon interaction with lipids. Two additional features contribute to resistance to TLFs: reduction of sensitivity to APOL1 requiring cysteine protease activity, and TbHpHbR inactivation due to a L210S substitution. According to such a multifactorial defence mechanism, transgenic expression of T. b. brucei TbHpHbR in T. b. gambiense did not cause parasite lysis in normal human serum. However, these transgenic parasites were killed in hypohaptoglobinaemic serum, after high TLF-1 uptake in the absence of haptoglobin (Hp) that competes for Hb and receptor binding. TbHpHbR inactivation preventing high APOL1 loading in hypohaptoglobinaemic serum may have evolved because of the overlapping endemic area of T. b. gambiense infection and malaria, the main cause of haemolysis-induced hypohaptoglobinaemia in western and central Africa.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Uzureau, Pierrick
Uzureau, Sophie
Lecordier, Laurence
Fontaine, Frederic
Tebabi, Patricia
Homble, Fabrice
Grelard, Axelle
Zhendre, Vanessa
Nolan, Derek P.
Lins, Laurence  ;  Université de Liège - ULiège > Chimie et bio-industries > Biophysique moléc. numér.
Crowet, Jean-Marc ;  Université de Liège - ULiège > Chimie et bio-industries > Biophysique moléc. numér.
Pays, Annette
Felu, Cecile
Poelvoorde, Philippe
Vanhollebeke, Benoit
Moestrup, Soren K.
Lyngso, Jeppe
Pedersen, Jan Skov
Mottram, Jeremy C.
Dufourc, Erick J.
Perez-Morga, David
Pays, Etienne
More authors (12 more) Less
Language :
Title :
Mechanism of Trypanosoma brucei gambiense resistance to human serum.
Publication date :
Journal title :
Publisher :
Nature Publishing Group, London, United Kingdom
Volume :
Issue :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi


Number of views
67 (7 by ULiège)
Number of downloads
0 (0 by ULiège)

Scopus citations®
Scopus citations®
without self-citations


Similar publications

Contact ORBi