Navegando por Autor "Matta, Maria Adelaide do Valle"
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Item Development of chronic cardiomyopathy in canine Chagas disease correlates with high IFN-g, TNF-a, and low IL-10 production during the acute infection phase.(2009) Guedes, Paulo Marcos da Matta; Veloso, Vanja Maria; Afonso, Luís Carlos Crocco; Caliari, Marcelo Vidigal; Carneiro, Cláudia Martins; Diniz, Lívia de Figueiredo; Silva, Eduardo de Almeida Marques da; Caldas, Ivo Santana; Matta, Maria Adelaide do Valle; Souza, Sheler Martins de; Lana, Marta de; Chiari, Egler; Galvão, Lúcia Maria da Cunha; Bahia, Maria TerezinhaWhen infected with Trypanosoma cruzi, Beagle dogs develop symptoms similar to those of Chagas disease in human beings, and could be an important experimental model for a better understanding of the immunopathogenic mechanisms involved in chronic chagasic infection. This study evaluates IL-10, IFN-g and TNF-a production in the sera, culture supernatant, heart and cervical lymph nodes and their correlation with cardiomegaly, cardiac inflammation and fibrosis in Beagle dogs infected with T. cruzi. Pathological analysis showed severe splenomegaly, lymphadenopathy and myocarditis in all infected dogs during the acute phase of the disease, with cardiomegaly, inflammation and fibrosis observed in 83% of the animals infected by T. cruzi during the chronic phase. The data indicate that infected animals producing IL-10 in the heart during the chronic phase and showing high IL-10 production in the culture supernatant and serum during the acute phase had lower cardiac alterations (myocarditis, fibrosis and cardiomegaly) than those with high IFN-g and TNF-a levels. These animals produced low IL-10 levels in the culture supernatant and serum during the acute phase and did not produce IL-10 in the heart during the chronic phase of the disease. Our findings showed that Beagle dogs are a good model for studying the immunopathogenic mechanism of Chagas disease, since they reproduce the clinical and immunological findings described in chagasic patients. The data suggest that the development of the chronic cardiac form of the disease is related to a strong Th1 response during the acute phase of the disease, while the development of the indeterminate form results from a blend of Th1 and Th2 responses soon after infection, suggesting that the acute phase immune response is important for the genesis of chronic cardiac lesions.Item Increased type 1 chemokine expression in experimental Chagas disease correlates with cardiac pathology in Beagle dogs.(2010) Guedes, Paulo Marcos da Matta; Veloso, Vanja Maria; Silva, André Talvani Pedrosa da; Diniz, Lívia de Figueiredo; Caldas, Ivo Santana; Matta, Maria Adelaide do Valle; Silva, Juliana Santiago; Chiari, Egler; Galvão, Lúcia Maria da Cunha; Silva, João Santana da; Bahia, Maria TerezinhaChemokines and chemokine receptors interaction have presented important role in leukocyte migration to specific immune reaction sites. Recently, it has been reported that chemokine receptors CXC (CXCR3) and CC (CCR5) were preferentially expressed on Th1 cells while CCR3 and CCR4 were preferentially expressed on Th2 cells. This study evaluated the mRNA expression of type 1 and type 2 chemokine and chemokine receptors in the cardiac tissue of Beagle dogs infected with distinct genetic groups of Trypanosoma cruzi (Y, Berenice- 78 and ABC strains) during acute and chronic phases. To analyze the correlation between chemokine and chemokine receptors expression and the development of heart pathology, the chronic infected animals were divided into groups, according to the parasite strain and based on the degree of heart damage: cardiac and indeterminate form of Chagas disease. Our results indicated that cardiac type1/2 chemokines and their receptors were partially dependent on the genetic diversity of parasites as well as the polarization of clinical forms. Also, dogs presenting cardiac form showed lower heart tissue mRNA expression of CCL24 (type 2) and higher expression of CCL5, CCL4 and CXCR3 (type 1) when compared with those with indeterminate form of disease. Together, these data reinforce a close-relation between T. cruzi genetic population and the host specific type 1 immune response and, for the first time, we show the distribution of type 1/2 chemokines associated with the development of cardiac pathology using dogs, a well similar model to study human Chagas disease.Item Inflammation enhances the risks of stroke and death in chronic chagas disease patients.(2016) Guedes, Paulo Marcos da Matta; Andrade, Cléber Mesquita de; Nunes, Daniela Ferreira; Pereira, Nathalie de Sena; Queiroga, Tamyres Bernadete Dantas; Coelho, George Luiz Lins Machado; Nascimento, Manuela Sales Lima; Matta, Maria Adelaide do Valle; Câmara, Antônia Cláudia Jácome da; Chiari, Egler; Galvão, Lúcia Maria da CunhaIschemic strokes have been implicated as a cause of death in Chagas disease patients. Inflammation has been recognized as a key component in all ischemic processes, including the intravascular events triggered by vessel interruption, brain damage and repair. In this study, we evaluated the association between inflammatory markers and the death risk (DR) and stroke risk (SR) of patients with different clinical forms of chronic Chagas disease. The mRNA expression levels of cytokines, transcription factors expressed in the adaptive immune response (Th1, Th2, Th9, Th17, Th22 and regulatory T cell), and iNOS were analyzed by realtime PCR in peripheral blood mononuclear cells of chagasic patients who exhibited the indeterminate, cardiac, digestive and cardiodigestive clinical forms of the disease, and the levels of these transcripts were correlated with the DR and SR. Cardiac patients exhibited lowermRNA nexpression levels of GATA-3, FoxP3, AHR, IL-4, IL-9, IL-10 and IL 22 but exhibited higher expression of IFN-γ and TNF-α compared with indeterminate patients. Digestive patients showed similar levels of GATA-3, IL-4 and IL-10 than indeterminate patients. Cardiodigestive patients exhibited higher levels of TNF-α compared with indeterminate and digestive patients. Furthermore, we demonstrated that patients with high DR and SR exhibited lower GATA-3, FoxP3, and IL-10 expression and higher IFN-γ, TNF-α and iNOS mRNA expression than patients with low DR and SR. A negative correlation was observed between Foxp3 and IL-10 mRNA expression and the DR and SR. Moreover, TNF-α and iNOS expression was positively correlated with DR and SR. Our data suggest that an inflammatory imbalance in chronic Chagas disease patients is associated with a high DR and SR. This study provides a better understanding of the stroke pathobiology in the general population and might aid the development of therapeutic strategies for controlling the morbidity and mortality of Chagas disease.Item Naturally Leishmania infantum-infected dogs display an overall impairment of chemokine and chemokine receptor expression during visceral leishmaniasis.(2013) Nascimento, Manuela Sales Lima; Albuquerque, Talyta Delfino Rolim de; Matta, Maria Adelaide do Valle; Caldas, Ivo Santana; Diniz, Lívia de Figueiredo; Silva, André Talvani Pedrosa da; Bahia, Maria Terezinha; Andrade, Cléber Mesquita de; Galvão, Lúcia Maria da Cunha; Câmara, Antônia Cláudia Jácome da; Guedes, Paulo Marcos da MattaDogs are the primary reservoir for Leishmania parasites. The immune response induced by Leishmania infantum infection in these animals has not been completely elucidated, and few studies have investigated the relationship between the expression levels of chemokines and chemokine receptors and the clinical status of dogs with canine visceral leishmaniasis (CVL). The aim of this study was to correlate the clinical status of naturally L. infantuminfected dogs (from rural areas of Mossoró city, State of Rio Grande do Norte, Brazil) with the expression levels of chemokines (ccl1, ccl2, ccl3, ccl4, ccl5, ccl17, ccl20, ccl24, ccl26, cxcl9, cxcl10) and chemokine receptors (cxcr3, ccr3, ccr4, ccr5, ccr6, ccr8) in the liver and spleen determined using real-time PCR. Twenty-one dogs were clinically evaluated and classified as asymptomatic (n = 11) or symptomatic (n = 10). Splenomegaly, weight loss and onychogryphosis were the most pronounced symptoms. In the liver, the mRNA expression levels of ccl1, ccl17, ccl26, ccr3, ccr4, ccr5, ccr6, and ccr8 were lower in symptomatic animals than in asymptomatic animals. Compared with uninfected animals, symptomatic dogs had lower expression levels of almost all molecules analyzed. Moreover, high clinical scores were negatively correlated with ccr5 and ccr6 expression and positively correlated with cxcl10 expression. We conclude that the impairment of the expression of chemokines and chemokine receptors results in deficient leukocyte migration and hampers the immune response, leading to the development of disease.