Sulfotopes from Trypanosoma cruzi major or minor antigenic glycoproteins, are involved in parasite infection, and immunopathogenesis of experimental Chagas disease

LUCIANA L. SOPRANO; ALICIA S. COUTO ; VILMA G DUSCHAK

Berlin

Congreso; Infectious Congress 2020 ans Tropical Diseases 2020; 2020

Statement of the Problem.Chagas disease (ChD) constitutes a major endemic health problem in Latin America. The presence of sulfate-bearing-glycoproteins has been identified in Trypanosoma cruzi, they are targets of specific immune responses and subjects chronically infected with T. cruzi mount specific humoral immune responses to sulfated glycoproteins. Cruzipain (Cz), a major antigen. containing a C-terminal domain (C-T), is responsible for the immunogenicity of the molecule in natural and experimental infection Synthetic anionic sugar conjugates containing N-acetyl D glucosamine-6-sulfate (NAcGlc6-SO3) mimics the N-glycan-linked sulfated epitope (sulfotope) displayed in the C-T. IgG2 antibody levels specific for sulfotopes are inversely correlated with Chagas disease severity. Another sulfated glycoprotein with serinecarboxypeptidase (SCP) activity was studied. Methodology & Theoretical Orientation: Native SCP co-purifies with Cz from Concanavalin-A affinity columns. The Cz-SCP mixture was desulfated, ascribing the cross-reactivity between both molecules to the presence of sulfated groups. SCP-N-glycosydic chains were analyzed by UV-MALDI-TOF-MS. Immunobloting of lysates from the different parasite stages were confronted with SO3-specific antibodies; in vivo effects of sodium chlorate on Cz-sulfation and tissue damage in C-T-immunized-mice muscle-tissues were evaluated. Findings: I) The presence of short-sulfated high-mannose-type oligosaccharidic chains was confirmed in SCP II) sulfotopes participate in trypomastigotes infection of cardiac cells; iii) sulfotopes generate muscle tissue damage in BALB/c mice, in absence of infection. iv) sulfotopes from Cz and other sulfated glycoproteins participate in parasite infection and immunopathogenesis. v) Sulfotopes and their specific antibodies are responsible for the ultrastructural abnormalities observed in the outcome of the experimental ChD disease vi) a band with apparent molecular weight similar to SCP was highly recognized in trypomastigotes: vi) SCP is a minor antigen recognized by most of chronic-Chagas-disease-patient´s sera. Conclusion & Significance. The shared sulfotopes between Cz and SCP, and the enhanced presence of sulfotopes in trypomastigotes, are involved in parasite-host relationship, in immunopathogenic and infection processes