Research Article: Trypanosoma cruzi Infection through the Oral Route Promotes a Severe Infection in Mice: New Disease Form from an Old Infection?

Date Published: June 19, 2015

Publisher: Public Library of Science

Author(s): Juliana Barreto-de-Albuquerque, Danielle Silva-dos-Santos, Ana Rosa Pérez, Luiz Ricardo Berbert, Eliane de Santana-van-Vliet, Désio Aurélio Farias-de-Oliveira, Otacilio C. Moreira, Eduardo Roggero, Carla Eponina de Carvalho-Pinto, José Jurberg, Vinícius Cotta-de-Almeida, Oscar Bottasso, Wilson Savino, Juliana de Meis, Helton da Costa Santiago.

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 5×104 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 GIversusOI 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.

Partial Text: Chagas disease (American trypanosomiasis), caused by the protozoan Trypanosoma cruzi, affects 6–7 million people worldwide, with an annual incidence of 28 thousand cases in the Americas [WHO, 2015]. Chagas disease is endemic in 21 countries in Latin America and was previously confined to this region. However, it has spread to other continents due to the migration of infected people [1]. Transmission to humans occurs through excreta deposition after biting of contaminated insect vectors belonging to the Reduviidae family, blood transfusion, organ transplantation, laboratory accident as well as congenitally and orally [2,3].

Currently, oral transmission of Chagas disease is the most important route of transmission in Brazil (70–80% of cases) [7]. Venezuela, Colombia, Bolivia, Argentina and Ecuador have also reported to have acute cases of Chagas disease associated with food/beverage consumption, but a significant study in the region is lacking [5]. These orally infected patients progress with a highly symptomatic disease (fever, facial edema, exanthema, hemorrhage, meningoencephalitis, abdominal pain, others), beyond the classical cardiac involvement. Additionally, increased mortality rate is marked in the first 2 weeks (8–35%), surpassing the calculated mortality produced by the disease resulting from the biting of infected insect vectors (5–10%) [18].



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