PROAPOPTOTIC ACTIVITY OF A TRYPANOSOMA-CRUZI CERAMIDE-CONTAINING GLYCOLIPID TURNED ON IN HOST MACROPHAGES BY IFN-GAMMA

The effects of glycoinositolphospholipid (GIPL), from the pathogenic p rotozoan Trypanosoma cruzi, and its isolated glycan and lipid (dihydro ceramide) components, were investigated in J774 cells and primary macr ophages. Isolated GIPL ceramide, but not intact GIPL or its glycan, in duced intense fluid phase endocytosis when added exogenously. In the p resence of the cytokine IFN-gamma, GIPL ceramide induced marked apopto sis in J774 cells and macrophages, independent of nitric oxide secreti on. When cells were preincubated with the GIPL-derived glycan chain, a ddition of intact GIPL induced macrophage apoptosis in the presence of IFN-gamma, Synthetic C-2-dihydroceramide also induced apoptosis in th e presence of IFN-gamma. Induction of apoptosis in T. cruzi-infected m acrophages by GIPL ceramide plus IFN-gamma led to increased parasite r elease compared with IFN-gamma treatment alone. Viable parasites relea sed comprised both infective trypomastigote and spheromastigote forms. These results identify a novel pathway by which T. cruzi glycosylphos phatidylinositol family molecules affect host macrophages, with implic ations for the infectious process.