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.
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References
Laveran, A. C. R. Acad. Sci. 134, 735–739 (1902).
Tytler, E. et al. Mol. Biochem. Parasitol. 62, 9–17 (1995).
Smith, A. B., Esko, J. D. & Hajduk, S. L. Science 268, 284–286 (1995).
Smith, A. B. & Hajduk, S. L. Proc. Natl Acad. Sd. USA 92, 10262–10266 (1995).
Smith, A. B., Doerner, M., Graham, A., Rotman, H., Vanacova, S. & Hajduk, S. L. Molec. Biochem. Parasitol.
Rifkin, M. R. Proc. Natl Acad. Sci. USA 75, 3450–3454 (1978).
Owen, J. S. & Gillett, M. P. T. Biochem. Soc. Trans. 15, 478–479 (1987).
Hajduk, S. L. et al. J. Biol. Chem. 264, 5210–5217 (1989).
Hawking, F. Trans. R. Soc. Trap. Med. Hyg. 90, 504–512 (1976).
Lorenz, P., James, R. W., Owen, J. S. & Betschart, B. Mol. Biochem. Parasitol. 64, 153–164 (1994).
Raper, J., Nussenzweiz, V. & Tomlinson, S. J. Exp. Med. 183, 1023–1029 (1996).
Tomlinson, S. et al. Mol. Biochem. Parasitol. 70, 131–138 (1995).
Hager, K. et al. J. Cell Biol. 126, 155–167 (1994).
Hoare, C. A. The Trypanosomes of Mammals: A Zoological Monograph (Blackwell Scientific, Oxford, 1972).
Mathieu-Daude, F. & Tibayrenc, M. Exp. Parasitol. 78, 1–19 (1994).
Rickman, L. & Kolala, S. L. Trans. R. Soc. Trop. Med. Hyg. 74, 817–819 (1980).
De Greef, C., Imberechts, H., Matthyssens, G., van Merivenne, N. & Hamers, R. Mol. Biochem. Parasitol. 36, 169–176 (1989).
De Greef, C. & Hamers, R. Mol. Biochem. Parasitol. 68, 277–284 (1994).
Rifkin, M. R., De Greef, C., Jiwa, A., Landsbrger, F. R. & Shapiro, S. Z. Mol. Biochem. Parasitol. 66, 211–220 (1994).
Cross, G. A. M. Annu. Rev. Immunol. 8, 83–110 (1990).
Oritz, J. C., Sechelski, J. B. & Seed, J. R. J. Parasitol. 80, 550–557 (1994).
Bangs, J. D., Hereld, D., Krakow, J. L., Hart, G. W. & England, P. T. Proc. Natl Acad. Sci. USA 82, 3208–3211 (1985).
Moore, D. R. et al. Exp. Parasitol. 81, 216–226 (1995).
Overath, P., Chaudri, M., Steverding, D. & Ziegelbauer, K. Parasitol. Today 10, 53–58 (1994).
Priest, J. M. & Hajduk, S. L. Mol. Biochem. Parasitol. 65, 294–304 (1994).
Lanham, S. N. Nature 218, 1273–1274 (1968).
Salmon, D. et al. Cell 78, 75–86 (1994).
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Hager, K., Hajduk, S. Mechanism of resistance of African trypanosomes to cytotoxic human HDL. Nature 385, 823–826 (1997). https://doi.org/10.1038/385823a0
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DOI: https://doi.org/10.1038/385823a0
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