Nature 385, 823 - 826 (27 February 1997); doi:10.1038/385823a0

Mechanism of resistance of African trypanosomes to cytotoxic human HDL

Kristin M. Hager^* & Stephen L. Hajduk

Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Schools of Medicine and Dentistry, Birmingham, Alabama 35294-0005, USA
^*Present address: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6018, USA.

Trypanosoma brucei brucei, the causative agent of ngana in cattle, is non-infectious to humans because of its sensitivity to the cytolytic activity of normal human serum¹. The toxin in normal human serum is human haptoglobin-related protein (Hpr)^2–5 which is found either as an apolipoprotein associated with a minor subclass of high-density lipoprotein (HDL), named trypanosome lytic factor (TLF1)^6–8, or as an unstable, high-molecular-mass protein complex known as TLF2 (refs 5, 9–12). TLF-mediated lysis of T. b. brucei requires binding, internalization and lysosomal targeting¹³. The human sleeping-sickness trypanosome, Trypanosoma brucei rhodesiense is resistant to TLF. Our studies reveal that resistant trypanosomes fail to endocytose TLF yet continue to bind TLF through cell-surface receptors. On the basis of these results, we conclude that one mechanism of resistance of human sleeping-sickness trypanosomes to human serum is decreased internalization of receptor-bound TLF.

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