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 parasite entry by inducing tyrosine phosphorylation of MAP kinase. Preincubation of human macrophages with r-gp83 transsialidase significantly enhanced both the percentage of phagocytosed trypanosomes and the number of trypanosomes per cell in a concentration dependent fashion. Incubation of r.gp83 with macrophages induced tyrosine phosphorylation of several macrophage proteins. This enhancement was inhibited by genistein, a tyrosine kinase inhibitor. The r-trypanosome ligand enhanced tyrosine phosphorylation of ERK1 and this enhancement was specifically inhibited by the inhibitor of MAP kinase phosphorylation, PD 98059, or by genistein. PD 98050 or genistein also inhibited the enhancement of trypomastigote 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.