Abstract
Digestive and cardiodigestive forms of Chagas' disease are observed in 2% to 27% of the patients, depending on their geographic location, Trypanosoma cruzi strain and immunopathological responses. The aim of this work was to evaluate the role of NOD2 innate immune receptor in the pathogenesis of the digestive system in Chagas' disease. Patients with digestive form of the disease showed lower mRNA expression of NOD2, higher expression of RIP2 and α-defensin 6, compared to indeterminate form, detected by Real-time PCR in peripheral blood mononuclear cells. In addition, there was a negative correlation between the expression of NOD2 and the degree of dilation of the esophagus, sigmoid and rectum in those patients. The infection of NOD2-/- mice with T. cruzi strain isolated from the digestive patient induced a decrease in intestinal motility. Histopathological analysis of the colon and jejunum of NOD2-/- and wild type C57BL/6 animals revealed discrete inflammatory foci during the acute phase of infection. Interestingly, during the chronic phase of the infection there was inflammation and hypertrophy of the longitudinal and circular muscular layer more pronounced in the colon and jejunum from NOD2-/- animals, when compared to wild type C57BL/6 mice. Together, our results suggest that NOD2 plays a protective role against the development of digestive form of Chagas' disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Animals
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Brazil
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Chagas Disease / immunology*
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Chagas Disease / pathology
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Colon / microbiology
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Colon / pathology
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Disease Models, Animal
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Female
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Humans
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Immunity, Innate
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Middle Aged
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Nod2 Signaling Adaptor Protein / genetics*
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Nod2 Signaling Adaptor Protein / immunology*
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Nod2 Signaling Adaptor Protein / metabolism*
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Receptor-Interacting Protein Serine-Threonine Kinase 2 / genetics
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Receptor-Interacting Protein Serine-Threonine Kinase 2 / metabolism
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Trypanosoma cruzi / immunology*
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Young Adult
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alpha-Defensins / genetics
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alpha-Defensins / metabolism
Substances
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DEFA6 protein, human
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NOD2 protein, human
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Nod2 Signaling Adaptor Protein
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Nod2 protein, mouse
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alpha-Defensins
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RIPK2 protein, human
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Receptor-Interacting Protein Serine-Threonine Kinase 2
Grants and funding
This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq/MS/SCTIE/DECIT grant no. 466698/2014-3, MCT/CNPq) and financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001. The author (PMMG) receives a scientific productivity scholarship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.