Alterations induced in the immune system by the trans-sialidase from Trypanosoma cruzi

MUCCI JUAN; RISSO MARIKENA; TRIBULATTI VIRGINIA; LEGUIZAMÓN M SUSANA; CAMPETELLA OSCAR

Buenos Aires, Argentina

Simposio; Simposio Internacional “Molecular Immunology of Protozoan Infections”; 2007

Howard Hughes Medical Institute

Trypanosoma cruzi, the causative agent of Chagas disease, is unable to synthesize sialic acids de novo. Instead, the parasite expresses the trans-sialidase, a modified sialidase that transfers the residue among glycoconjugates. It allows the acquisition of the residue from the host sialylated molecules. The enzyme is a virulence factor located at the parasite surface but it is also shed to the milieu being detected in blood. At the parasite surface, the enzyme is involved in i) the evasion of lysis by seric factors, ii) interaction/invasion of the host cell and iii) escape from the parasitophore vesicle into the cytoplasm. The systemic distribution through the bloodstream enables the enzyme to act far from the infection sites. Our lab examines the effect of the circulating enzyme on the immune system in vivo. We found that the enzyme is associated with some of the major alterations observed during the acute phase of the infection. The intravenous injection of the enzyme mimics findings from the acute infection such as apoptosis induction in cell components of thymus, spleen and ganglia and thrombocytopenia. These alterations were prevented during infections through the passive administration of either rabbit or monoclonal antibodies. In the thymus, the enzyme induces the CD4+CD8+ thymocyte depletion observed during the infection. The trans-sialidase not only mediates the transfer but also the hydrolysis, although at a very lesser efficiency rate, of the sialyl residue. We analyzed which activity was associated with the pathogenic events and found that the desialylation induces thrombocytopenia meanwhile the apoptosis of cells from the immune system is associated with the transference of the residue. Since this activity is not present in mammals and constitutes a central virulence factor in the pathogenesis of the disease, it seems to be a putative target for the development of inhibitors to be used in chemotherapy.