Activity of human trypanosome lytic factor in mice

The inability of the cattle pathogen Trypanosoma brucei brucei to infect hu mans is due to an innate factor in human serum termed Trypanosome Lytic Fac tor (TLF). Human haptoglobin-related protein is the proposed toxin in TLF a nd can exist either as a component of a minor subclass of high-density lipo protein (TLF-1) or as a lipid free, high molecular weight protein complex ( TLF-2). The trypanolytic activity of both TLF-1 and TLF-2 has been studied in vitro but their relative contributions to protection against T. b. bruce i infection in vivo has not been established. In the present studies we sho w that treatment of T. b brucei infected mice with TLF-1 resulted in a dose dependent decrease in parasite numbers but did not affect parasite numbers in mice infected with Trypanosoma brucei rhodesiense. the causative agent of the human sleeping sickness. Similarly, pretreatment of mice with TLF-1 resulted in protection against a challenge by T. b. brucei but had no effec t on T. b. rhodesiense challenge. Induction of the acute phase protein hapt oglobin, a natural antagonist of TLF-1. diminished but did not abolish the protection against trypanosome challenge. In addition, haptoglobin knockout mice showed higher levels of TLF-1 mediated protection against a T. b. bru cei challenge. These results suggest that while TLF-1 is active in vivo, ev en in the presence of elevated levels of haptoglobin, its activity is modul ated in a dose dependent fashion by haptoglobin in the circulation. (C) 200 1 Elsevier Science B.V. All rights reserved.