SIGNAL-TRANSDUCTION IN HUMAN MACROPHAGES BY GP83 LIGAND OF TRYPANOSOMA-CRUZI - TRYPOMASTIGOTE GP83 LIGAND UP-REGULATES TRYPANOSOME ENTRY THROUGH THE MAP KINASE PATHWAY

We found that Trypanosoma cruzi trypomastigote cloned surface ligand ( gp83 trans-sialidase) signals human macrophages to up-regulate parasit e entry by inducing tyrosine phosphorylation of MAP kinase. Preincubat ion of human macrophages with r-gp83 transsialidase significantly enha nced both the percentage of phagocytosed trypanosomes and the number o f trypanosomes per cell in a concentration dependent fashion. Incubati on of r-gp83 with macrophages induced tyrosine phosphorylation of seve ral macrophage proteins. This enhancement was inhibited by genistein, a tyrosine kinase inhibitor. The r-trypanosome ligand enhanced tyrosin e phosphorylation of ERK1 and this enhancement was specifically inhibi ted by the inhibitor of MAP kinase phosphorylation, PD 98059, or by ge nistein. PD 98050 or genistein also inhibited the enhancement of trypo mastigote uptake by macrophages induced by the r-ligand. These results indicate that T. cruzi uses a novel mechanism to signal cells in the process of trypanosome entry, via a secreted trypanosome ligand which signals macrophages through the MAP kinase pathway. (C) 1998 Academic press.