title: Trypanosoma cruzi Infection through the Oral Route Promotes a Severe Infection in Mice: New Disease Form from an Old Infection?
abstract: Oral transmission of Chagas disease has been documented in Latin American countries. Nevertheless, significant studies on the pathophysiology of this form of infection are largely lacking. The few studies investigating oral route infection disregard that inoculation in the oral cavity (Oral infection, OI) or by gavage (Gastrointestinal infection, GI) represent different infection routes, yet both show clear-cut parasitemia and heart parasitism during the acute infection. Herein, BALB/c mice were subjected to acute OI or GI infection using 5x10(4) culture-derived Trypanosoma cruzi trypomastigotes. OI mice displayed higher parasitemia and mortality rates than their GI counterparts. Heart histopathology showed larger areas of infiltration in the GI mice, whereas liver lesions were more severe in the OI animals, accompanied by higher Alanine Transaminase and Aspartate Transaminase serum contents. A differential cytokine pattern was also observed because OI mice presented higher pro-inflammatory cytokine (IFN-γ, TNF) serum levels than GI animals. Real-time PCR confirmed a higher TNF, IFN-γ, as well as IL-10 expression in the cardiac tissue from the OI group compared with GI. Conversely, TGF-β and IL-17 serum levels were greater in the GI animals. Immunolabeling revealed macrophages as the main tissue source of TNF in infected mice. The high mortality rate observed in the OI mice paralleled the TNF serum rise, with its inhibition by an anti-TNF treatment. Moreover, differences in susceptibility between GI versus OI mice were more clearly related to the host response than to the effect of gastric pH on parasites, since infection in magnesium hydroxide-treated mice showed similar results. Overall, the present study provides conclusive evidence that the initial site of parasite entrance critically affects host immune response and disease outcome. In light of the occurrence of oral Chagas disease outbreaks, our results raise important implications in terms of the current view of the natural disease course and host-parasite relationship.
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Barreto-de-Albuquerque
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Danielle
authors.initials: D
authors.lastname: Silva-dos-Santos
authors.affiliation: Immunology Institute, Faculty of Medical Science, National University of Rosario, Rosario, Argentina.
authors.forename: Ana Rosa
authors.initials: AR
authors.lastname: Pérez
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Luiz Ricardo
authors.initials: LR
authors.lastname: Berbert
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Eliane
authors.initials: E
authors.lastname: de Santana-van-Vliet
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Désio Aurélio
authors.initials: DA
authors.lastname: Farias-de-Oliveira
authors.affiliation: Laboratory on Molecular Biology and Endemic Diseases, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Otacilio C
authors.initials: OC
authors.lastname: Moreira
authors.affiliation: Immunology Institute, Faculty of Medical Science, National University of Rosario, Rosario, Argentina.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Roggero
authors.affiliation: Laboratory on Experimental Pathology, Immunobiology Department, Federal Fluminense University, Niteroi, Brazil.
authors.forename: Carla Eponina
authors.initials: CE
authors.lastname: de Carvalho-Pinto
authors.affiliation: National and International Laboratory on Triatomine Taxonomy, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: José
authors.initials: J
authors.lastname: Jurberg
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Vinícius
authors.initials: V
authors.lastname: Cotta-de-Almeida
authors.affiliation: Immunology Institute, Faculty of Medical Science, National University of Rosario, Rosario, Argentina.
authors.forename: Oscar
authors.initials: O
authors.lastname: Bottasso
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Wilson
authors.initials: W
authors.lastname: Savino
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: de Meis
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000276:immunology / Q000401:mortality / Q000635:transmission*; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000473:pathology; D018512:Parasitemia / Q000276:immunology / Q000401:mortality / Q000635:transmission; D014349:Trypanosoma cruzi / Q000276:immunology / Q000472:pathogenicity
chemical_list: D016207:Cytokines