Trypanosoma cruzi infection through the oral route promotes a severe infection in mice: new disease form from an old infection?

J BARRETO-DE-ALBUQUERQUE; D SILVA-DOS-SANTOS; ANA ROSA PEREZ; L R BERBERT; E DE SANTANA-VAN-VLIET; D FARIAS DE OLIVEIRA; O MOREIRA; E A ROGGERO; CE DE CARVALHO-PINTO; J JURBERG; V COTTA-DE-ALMEIDA; O BOTTASSO, ; W SAVINO; J DE MEIS

PLOS NEGLECTED TROPICAL DISEASES

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2015 vol. 9 p. 1 - 21

1935-2735

Oral transmission of Chagas? disease has been documented in Latin American countries, with current evidence indicating to be nowadays the most important infection route in the Brazilian Amazon region. Most knowledge concerning the immunology of Chagas? disease derives from studies in mice infected intraperitoneally or by the subcutaneous route. The few studies using oral route infection disregard that inoculation in the oral cavity (Oral infection, OI) or by gavage (gastrointestinal infection, GI) represent different infection routes, as yet both show clear-cut parasitemia and heart parasitism during the acute infection. Accordingly, BALB/c mice were herein subjected to acute OI or GI infection, using trypomastigotes (Tulahuén strain). As a result, for the first time, it is being reported that OI mice displayed significantly higher parasitemia and mortality rates than their GI counterparts. Heart histopathology showed extensive infiltrates in GI mice, while liver lesions are more severe in OI animals, accompanied by higher ALanine Transaminase and ASpartate Transaminase serum contents. A differential cytokine pattern was also seen by multiplex analysis, revealing that 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 gene expression in the cardiac tissue from OI group, compared to GI mice. Conversely, TGF-β serum levels were greater in GI animals. Interestingly, the high mortality rate seen in OI mice paralleled the TNF serum rise, with its inhibition by an anti-TNF treatment resulting in a significantly improved disease outcome. 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, through the oral cavity or more directly to the gastrointestinal tract, critically affects the 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 natural disease course and the particular host-parasite relationship established upon differential exposures.