%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Vanhollebeke, B.
%A Nielsen, M. J.
%A Watanabe, Y.
%A Truc, Philippe
%A Vanhamme, L.
%A Nakajima, K.
%A Moestrup, S. K.
%A Pays, E.
%T Distinct roles of haptoglobin-related protein and apolipoprotein L-1 in trypanolysis by human serum
%D 2007
%L fdi:010037938
%G ENG
%J Proceedings of the National Academy of Sciences of the United States of America
%@ 0027-8424
%K innate immunity ; sleeping sickness ; trypanolytic factor ; haptoglobin receptor ; Trypanosoma brucei
%M CC:0002449724-0080
%N 10
%P 4118-4123
%R 10.1073/pnas.0609902104
%U https://www.documentation.ird.fr/hor/fdi:010037938
%> https://horizon.documentation.ird.fr/exl-doc/pleins_textes/2024-12/010037938.pdf
%V 104
%W Horizon (IRD)
%X Apolipoprotein L-I (apoL-I) is a human high-density lipoprotein (HDL) component able to kill Trypanosoma brucei brucei by forming anion-selective pores in the lysosomal membrane of the parasite. Another HDL component, haptoglobin-related protein (Hpr), has been suggested as an additional toxin required for full trypanolytic activity of normal human serum. We recently reported the case of a human lacking apoL-I (apoL-I-/-HS) as the result of frameshift mutations in both apoL-I alleles. Here, we show that this serum, devoid of any trypanolytic activity, exhibits normal concentrations of HDL-bound Hpr. Conversely, the serum of individuals with normal HDL-bound apoL-I but who lack Hpr and haptoglobin [Hp(r)-/-HS] as the result of gene deletion (anhaptoglobinemia) exhibited phenotypically normal but delayed trypanolytic activity. The trypanolytic properties of Hp(r)-/-HS were mimicked by free recombinant apoL-I, whereas recombinant Hpr did not affect trypanosomes. The lysis delay observed with either Hp(r)-/-HS or recombinant apoL-I could entirely be attributed to a defect in the uptake of the lytic components. Thus, apoL-I is responsible for the trypanolytic activity of normal human serum, whereas Hpr allows fast uptake of the carrier HDL particles, presumably through their binding to an Hp/Hpr surface receptor of the parasite.
%$ 052