Costimulation of host T lymphocytes by a trypanosomal trans-sialidase:: Involvement of CD43 signaling

Trans-sialidase is a membrane-bound and shed sialidase from Trypanosoma cruzi, the protozoan parasite responsible for Chagas disease. We investigated the role of soluble trans-sialidase on host CD4(+) T cell activation. Trans-sialidase activated naive CD4(+) T cells in vivo. Both enzymatically active and inactive recombinant trans-sialidases costimulated CD4(+) T cell activation in vitro. Costimulation resulted in increased mitogen-activated protein kinase activation, proliferation, and cytokine synthesis. Furthermore, active and inactive trans-sialidases blocked activation-induced cell death in CD4(+) T cells from T. cruzi-infected mice. By flow cytometry, inactive trans-sialidase bound the highly, sialylated surface Ag CD43 on host CD4(+) T cells. Both costimulatory and antiapoptotic effects of trans-sialidases required CD43 signaling. These results suggest that trans-sialidase family, proteins are involved in exacerbated host T lymphocyte responses observed in T. cruzi infection.