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

dc.citation.titlePLOS Neglected Tropical Diseaseses
dc.citation.volumePLoS Negl Trop Dis 9(6): e0003849es
dc.creatorBarreto-de-Albuquerque, Juliana
dc.creatorSilva-dos-Santos, Danielle
dc.creatorPérez, Ana Rosa
dc.creatorBerbert, Luiz Ricardo
dc.creatorde Santana-van-Vliet, Eliane
dc.creatorFarias-de-Oliveira, Désio Aurélio
dc.creatorMoreira, Otacilio C.
dc.creatorRoggero, Eduardo
dc.creatorde Carvalho-Pinto, Carla Eponina
dc.creatorJurberg, José
dc.creatorCotta-de-Almeida, Vinícius
dc.creatorBottasso, Oscar
dc.creatorSavino, Wilson
dc.creatorde Meis, Juliana
dc.date.accessioned2015-08-13T13:26:45Z
dc.date.available2015-08-13T13:26:45Z
dc.date.issued2015-06-19
dc.descriptionOral 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 5x104 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.es
dc.description.filFil: Pérez, Ana Rosa. Immunology Institute, Faculty of Medical Science, National University of Rosario, Rosario, Argentinaes
dc.description.filFil: Roggero, Eduardo. Immunology Institute, Faculty of Medical Science, National University of Rosario, Rosario, Argentinaes
dc.description.filFil: Bottasso, Oscar. Immunology Institute, Faculty of Medical Science, National University of Rosario, Rosario, Argentinaes
dc.description.sponsorshipThis work was supported by the Rio de Janeiro State Research Foundation (FAPERJ-Grant E-26/103.249/2011) and Brazilian National Research Council (CNPq-Grant 479431/2011-6) to JdM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.es
dc.formatapplication/pdf
dc.format.extent1-21es
dc.identifier.issn1935-2735es
dc.identifier.urihttp://hdl.handle.net/2133/4879
dc.language.isoenges
dc.publisherPLOS (Public Library of Science)es
dc.relation.publisherversiondoi:10.1371/journal.pntd.0003849es
dc.rightsopenAccesses
dc.rights.holder© 2015 Barreto-de-Albuquerque et al.es
dc.rights.textThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.es
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.sourcePLOS Neglected Tropical Diseaseses
dc.subjectGenitourinary infectionses
dc.subjectParasitic diseaseses
dc.subjectTrypanosoma cruzies
dc.subjectGastrointestinal infectionses
dc.subjectHeartes
dc.subjectTrypomastigoteses
dc.subjectParasitemiaes
dc.titleTrypanosoma cruzi Infection through the Oral Route Promotes a Severe Infection in Mice: New Disease Form from an Old Infection?es
dc.typearticle
dc.typeartículo
dc.typepublishedVersion
dc.type.collectionarticulo

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