High-density lipoprotein-mediated lysis of trypanosomes

Nearly 90 years after the discovery that certain African trypanosornes were killed by normal human serum, we still do not understand how this innate trypanocidal factor works. Biochemical studies have provided us with an unlikely candidate: human high-density lipoprotein (HDL). This trypanosome lytic factor (TLF) from human serum is important since its activity restricts the host range of Trypanosoma brucei brucei, and the expression of this natural killing factor in cattle would represent a novel approach to the control of bovine tryponosomiasis. Here, Steve Hajduk, Kristin Hager and Jeffrey Esko discuss evidence for the TLF being a minor subclass of serum HDL and propose a mechanism for lysis based on the binding, endocytosis and lysosomal targeting of TLF.