Horizon 1 1 17 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES Proceedings of the National Academy of Sciences of the United States of America 4118-4123 innate immunity sleeping sickness trypanolytic factor haptoglobin receptor Trypanosoma brucei 2007 fdi:010037938 ENG Proceedings of the National Academy of Sciences of the United States of America 0027-8424 CC:0002449724-0080 10 10.1073/pnas.0609902104 https://www.documentation.ird.fr/hor/fdi:010037938 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/2024-12/010037938.pdf 104 Horizon (IRD) 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