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Mechanism of resistance of African trypanosomes to cytotoxic human HDL

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  • Kristin M. Hager

    (University of Alabama at Birmingham, Schools of Medicine and Dentistry
    University of Pennsylvania)

  • Stephen L. Hajduk

    (University of Alabama at Birmingham, Schools of Medicine and Dentistry)

Abstract

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.

Suggested Citation

  • Kristin M. Hager & Stephen L. Hajduk, 1997. "Mechanism of resistance of African trypanosomes to cytotoxic human HDL," Nature, Nature, vol. 385(6619), pages 823-826, February.
    • Handle: RePEc:nat:nature:v:385:y:1997:i:6619:d:10.1038_385823a0
    DOI: 10.1038/385823a0
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