title: Interaction with host factors exacerbates Trypanosoma cruzi cell invasion capacity upon oral infection.
abstract: Outbreaks of severe acute Chagas' disease acquired by oral infection, leading to death in some cases, have occurred in recent years. Using the mouse model, we investigated the basis of such virulence by analyzing a Trypanosoma cruzi isolate, SC, from a patient with severe acute clinical symptoms, who was infected by oral route. It has previously been shown that, upon oral inoculation into mice, T. cruzi metacyclic trypomastigotes invade the gastric mucosal epithelium by engaging the stage-specific surface glycoprotein gp82, whereas the surface molecule gp90 functions as a down-modulator of cell invasion. We found that, when orally inoculated into mice, metacyclic forms of the SC isolate, which express high levels of gp90, produced high parasitemias and high mortality, in sharp contrast with the reduced infectivity in vitro. Upon recovery from the mouse stomach 1h after oral inoculation, the gp90 molecule of the parasites was completely degraded, and their entry into HeLa cells, as well as into Caco-2 cells, was increased. The gp82 molecule was more resistant to digestive action of the gastric juice. Host cell invasion of SC isolate metacyclic trypomastigotes was augmented in the presence of gastric mucin. No alteration in infectivity was observed in T. cruzi strains CL and G which were used as references and which express gp90 molecules resistant to degradation by gastric juice. Taken together, our findings suggest that the exacerbation of T. cruzi infectivity, such as observed upon interaction of the SC isolate with the mouse stomach components, may be responsible for the severity of acute Chagas' disease that has been reported in outbreaks of oral T. cruzi infection.
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, Brazil.
authors.forename: Charles
authors.initials: C
authors.lastname: Covarrubias
authors.forename: Mauro
authors.initials: M
authors.lastname: Cortez
authors.forename: Daniele
authors.initials: D
authors.lastname: Ferreira
authors.forename: Nobuko
authors.initials: N
authors.lastname: Yoshida
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D002478:Cells, Cultured; D014355:Chagas Disease / Q000469:parasitology* / Q000635:transmission; D004063:Digestion; D005260:Female; D005750:Gastric Juice; D006367:HeLa Cells; D006790:Host-Parasite Interactions; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009059:Mouth Diseases / Q000469:parasitology*; D009077:Mucins / Q000494:pharmacology; D018512:Parasitemia / Q000469:parasitology; D010434:Pepsin A / Q000494:pharmacology; D015800:Protozoan Proteins / Q000378:metabolism; D016019:Survival Analysis; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000378:metabolism
chemical_list: D009077:Mucins; D015800:Protozoan Proteins; D014643:Variant Surface Glycoproteins, Trypanosoma; C044186:glycoprotein GP90, Trypanosoma cruzi; D010434:Pepsin A