Vanhollebeke B. auteur aut IRD Nielsen M. J. auteur aut IRD Watanabe Y. auteur aut IRD Truc Philippe auteur aut IRD Vanhamme L. auteur aut IRD Nakajima K. auteur aut IRD Moestrup S. K. auteur aut IRD Pays E. auteur aut IRD text journalArticle eng text/pdf reformatted digital access 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. specialized innate immunity sleeping sickness trypanolytic factor haptoglobin receptor Trypanosoma brucei 052 104 10 4118-4123 2007 0027-8424 https://www.documentation.ird.fr/hor/fdi:010037938 10.1073/pnas.0609902104 0027-8424 [F B010037938] https://www.documentation.ird.fr/hor/fdi:010037938 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/2024-12/010037938.pdf IRD - Base Horizon / Pleins textes 2007-06-01 2024-12-24 fdi:010037938 fre