Infection by the oral route is currently an important mode of transmission of Trypanosoma cruzi Latin American countries where the genetic group TcI is predominant, being responsible for frequent outbreaks of acute cases of Chagas disease, particulary in te Brazilian Amazon. Information on the molecular mechanisms of host cell invasion by T. cruzi strains of TcI lineage isolated from chagasic patients, as well as data on the course of infection by the oral route in the murine model, are still scarce. Therefore, in this project we aimed at the characterization of T. cruzi strains from chagasic patients, with focus on the molecular mechanisms involved in the process of host cell invasion by metacyclic trypomastigotes and on the establishment of infection in mice by the oral route. By using T. cruzi isolates from different geographical regions, we intend to:- Analyze the expression of metacyclic trypomastigotes surface molecules, in particular of gp90, gp82 and gp35/50. - Determine the cell invasion capacity of metacyclic forms. - Examine whether gp82 is involved in the process of target cell invasion by metacyclic forms. - Determine the effect of drugs that inhibit lysossomal exocytosis on host cell invasion by metacyclic forms. - Investigate which signaling pathways are activated in the parasites during cell invasion. - Examine the activity of cruzipain in metacyclic forms and determine whether the enzyme is involved in cell invasion. - Determine the susceptibility of metacyclic forms to degradation by pepsin. - Examine the capacity of migration of metacyclic forms through a gastric mucin layer. - Investigate the effect of gastric mucin in cell invasion by metacyclic forms. - Determine the course of infection in mice infected orally with metacyclic forms.- Analyze the degree of parasitism in the gastric mucosal epithelium of mice infected orally with metacyclic forms. - Determine the degree of parasitism in diverse organs of mice at the acute phase of infection upon oral administration of the degree of parasitism in the gastric mucosal epithelium of mice infected orally with metacyclic forms.
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