Distinct roles of haptoglobin-related protein and apolipoprotein L-1 in trypanolysis by human serum Vanhollebeke, B. Nielsen, M. J. Watanabe, Y. /Truc, Philippe Vanhamme, L. Nakajima, K. Moestrup, S. K. Pays, E. innate immunity sleeping sickness trypanolytic factor haptoglobin receptor Trypanosoma brucei 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. 2007 text https://www.documentation.ird.fr/hor/fdi:010037938 fdi:010037938 Vanhollebeke B., Nielsen M. J., Watanabe Y., Truc Philippe, Vanhamme L., Nakajima K., Moestrup S. K., Pays E.. Distinct roles of haptoglobin-related protein and apolipoprotein L-1 in trypanolysis by human serum. 2007, 104 (10), 4118-4123 EN