NOD2 receptor is crucial for protecting against the digestive form of Chagas disease

by Nathalie de Sena Pereira, Tamyres Bernadete Dantas Queiroga, Denis Dantas Silva, Manuela Sales Lima Nascimento, Cléber Mesquita de Andrade, Janeusa Trindade de Souto, Mayra Fernanda Ricci, Rosa Maria Esteves Arantes, Dario Simões Zamboni, Egler Chiari, Antônia Cláudia Jácome da Câmara, Lúcia Maria da Cunha Galvão, Paulo Marcos Matta Guedes

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.