Trypanosoma cruzi causes a suppression of the immune system leading to persistence in host cells. The trans-sialidase (TS) expressed by T. cruzi is a major virulence factor and transfers sialic acid from host glycoconjugates to mucin-like molecules on the parasite. Here we demonstrate that these sialylated structures play a role in the immunosuppression. We used two T. cruzi strains, whose TS-activity correlated with their pathogenicity. The Tulahuen strain, characterized by a high TS-activity efficiently infected mice, whereas the Tehuantepec strain showing a reduced TS-activity could not establish a patent parasitemia. In vitro analysis revealed that these two strains invaded phagocytic and non-phagocytic host cells at a comparable rate, but they exhibited different potentials to modulate dendritic cell (DC) function. In contrast to Tehuantepec, the Tulahuen strain suppressed the production of the proinflammatory cytokine IL-12 and subsequent T cell activation. This inhibitory effect was absent upon desialylation of the parasite. Therefore, we analyzed whether sialylated structures of T. cruzi interact with the inhibitory sialic acid-binding protein Siglec-E on DC. Indeed, Siglec-E interacted with the pathogenic Tulahuen strain, but showed a diminished binding to the Tehuantepec strain. Ligation of Siglec-E on DC using antibodies confirmed this inhibitory effect on DC function.
