BARBARA MARIA IANNI
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
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- Epigenetic regulation of transcription factor binding motifs promotes Th1 response in Chagas disease cardiomyopathy(2022) BROCHET, Pauline; IANNI, Barbara Maria; LAUGIER, Laurie; FRADE, Amanda Farage; NUNES, Joao Paulo Silva; TEIXEIRA, Priscila Camillo; MADY, Charles; FERREIRA, Ludmila Rodrigues Pinto; FERRE, Quentin; SANTOS, Ronaldo Honorato Barros; KURAMOTO, Andreia; CABANTOUS, Sandrine; STEFFEN, Samuel; STOLF, Antonio Noedir; POMERANTZEFF, Pablo; FIORELLI, Alfredo Inacio; BOCCHI, Edimar Alcides; PISSETTI, Cristina Wide; SABA, Bruno; CANDIDO, Darlan da Silva; DIAS, Fabricio C.; SAMPAIO, Marcelo Ferraz; GAIOTTO, Fabio Antonio; MARIN-NETO, Jose Antonio; FRAGATA, Abilio; ZANIRATTO, Ricardo Costa Fernandes; SIQUEIRA, Sergio; PEIXOTO, Giselle De Lima; RIGAUD, Vagner Oliveira-Carvalho; BACAL, Fernando; BUCK, Paula; ALMEIDA, Rafael Ribeiro; LIN-WANG, Hui Tzu; SCHMIDT, Andre; MARTINELLI, Martino; HIRATA, Mario Hiroyuki; DONADI, Eduardo Antonio; PEREIRA, Alexandre Costa; RODRIGUES JUNIOR, Virmondes; PUTHIER, Denis; KALIL, Jorge; SPINELLI, Lionel; CUNHA-NETO, Edecio; CHEVILLARD, ChristopheChagas disease, caused by the protozoan Trypanosoma cruzi, is an endemic parasitic disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including the often-fatal Chronic Chagasic Cardiomyopathy (CCC). Although previous studies have demonstrated some genetic deregulations associated with CCCs, the causes of their deregulations remain poorly described. Based on bulk RNA-seq and whole genome DNA methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. Analysis of heart tissue gene expression profile allowed us to identify 1407 differentially expressed transcripts (DEGs) specific from CCC patients. A tissue DNA methylation analysis done on the same tissue has permitted the identification of 92 regulatory Differentially Methylated Regions (DMR) localized in the promoter of DEGs. An in-depth study of the transcription factors binding sites (TFBS) in the DMRs corroborated the importance of TFBS's DNA methylation for gene expression in CCC myocardium. TBX21, RUNX3 and EBF1 are the transcription factors whose binding motif appears to be affected by DNA methylation in the largest number of genes. By combining both transcriptomic and methylomic analysis on heart tissue, and methylomic analysis on blood, 4 biological processes affected by severe CCC have been identified, including immune response, ion transport, cardiac muscle processes and nervous system. An additional study on blood methylation of moderate CCC samples put forward the importance of ion transport and nervous system in the development of the disease.
- Ebi3 Prevents Trypanosoma cruzi-Induced Myocarditis by Dampening IFN-gamma-Driven Inflammation(2017) MEDINA, Tiago Silva; OLIVEIRA, Gabriela Goncalves; SILVA, Maria Claudia; DAVID, Bruna Araujo; SILVA, Grace Kelly; FONSECA, Denise Morais; SESTI-COSTA, Renata; FRADE, Amanda Farage; BARON, Monique Andrade; IANNI, Barbara; PEREIRA, Alexandre Costa; CHEVILLARD, Christophe; CUNHA-NETO, Edecio; MARIN-NETO, Jose Antonio; SILVA, Joao SantanaThe identification of anti-inflammatory mediators can reveal important targetable molecules capable of counterbalancing Trypanosoma cruzi-induced myocarditis. Composed of Ebi3 and IL-27p28 subunits, IL-27 is produced by myeloid cells and is able to suppress inflammation by inducing IL-10-producing Tr1 cells, thus emerging as a potential candidate to ameliorate cardiac inflammation induced by T. cruzi. Although IL-27 has been extensively characterized as a suppressive cytokine that prevents liver immunopathogenesis after T. cruzi infection, the mechanisms underlying its effects on T. cruzi-induced myocarditis remain largely unknown. Here, wild-type (WT) and Ebi3-deficient animals were intraperitoneally infected with trypomastigotes of T. cruzi Y strain and used to evaluate the potential anti-inflammatory properties of Ebi3 during T. cruzi infection. The survival rates of mice were daily recorded, the frequency of inflammatory cells was analyzed by flow cytometry and inflammatory mediators were measured by ELISA, real-time PCR and PCR array. We reported that T. cruzi-induced myocarditis was prevented by Ebi3. Stressors mainly recognized by TLR2 and TLR4 receptors on myeloid cells were essential to trigger IL-27p28 production. In addition, Ebi3 regulated IFN-gamma-mediated myocarditis by promoting an anti-inflammatory environment through IL-10, which was most likely produced by Tr1 cells rather than classical regulatory T cells (Tregs), in the heart tissue of T. cruzi-infected animals. Furthermore, in vivo IFN-gamma blockade ameliorated the host survival without compromising the parasite control in the bloodstream. In humans, IL-27p28 was correlated with cardiac protection during Chagas disease. Patients with mild clinical forms of the disease produced high levels of IL-27p28, whereas lower levels were found in those with severe forms. In addition, polymorphic sites at Ebi3 gene were associated with severe cardiomyopathy in patients with Chagas disease. Collectively, we describe a novel regulatory mechanism where Ebi3 dampens cardiac inflammation by modulating the overproduction of IFN-gamma, the bona fide culprit of Chagas disease cardiomyopathy.
- Polymorphisms in Genes Affecting Interferon-gamma Production and Th1 T Cell Differentiation Are Associated With Progression to Chagas Disease Cardiomyopathy(2020) FRADE-BARROS, Amanda Farage; IANNI, Barbara Maria; CABANTOUS, Sandrine; PISSETTI, Cristina Wide; SABA, Bruno; LIN-WANG, Hui Tzu; BUCK, Paula; MARIN-NETO, Jose Antonio; SCHMIDT, Andre; DIAS, Fabricio; HIRATA, Mario Hiroyuki; SAMPAIO, Marcelo; FRAGATA, Abilio; PEREIRA, Alexandre Costa; DONADI, Eduardo; RODRIGUES, Virmondes; KALIL, Jorge; CHEVILLARD, Christophe; CUNHA-NETO, EdecioBackground:Chagas disease, caused by the protozoanTrypanosoma cruzi, is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is the most important clinical consequence ofT. cruziinfection, while the others remain asymptomatic (ASY). IFN-gamma and IFN-gamma-producing Th1-type T cells are increased in peripheral blood and CCC myocardium as compared to ASY patients, while the Th1-antagonizing cytokine IL-10 is more expressed in ASY patients. Importantly IFN-gamma-producing Th1-type T cells are the most frequent cytokine-producing T cell subset in CCC myocardium, while expression of Th1-antagonizing cytokines IL-10 and IL-4 is unaltered. The control of IFN-gamma production by Th1-type T cells may be a key event for progression toward CCC. A genetic component to disease progression was suggested by the familial aggregation of cases and the association of gene polymorphisms with CCC development. We here investigate the role of gene polymorphisms (SNPs) in several genes involved in the control of IFN-gamma production and Th1 T cell differentiation in CCC development. Methods:We studied a Brazilian population including 315 CCC cases and 118 ASY subjects. We assessed 35 Tag SNPs designed to represent all the genetic information contained in theIL12B, IL10, IFNG, andIL4genes. Results:We found 2IL12SNPs (rs2546893, rs919766) and a trend of association for aIL10SNP (rs3024496) to be significantly associated with the ASY group. these associations were confirmed by multivariate analysis and allele tests. The rs919766C, 12rs2546893G, and rs3024496C alleles were associated to an increase risk to CCC development. Conclusions:Our data show that novel polymorphisms affectingIL12BandIL10, but notIFNGorIL4genes play a role in genetic susceptibility to CCC development. This might indicate that the increased Th1 differentiation and IFN-gamma production associated with CCC is genetically controlled.
- Polymorphisms in Genes Affecting Interferon-gamma Production and Th1 T Cell Differentiation Are Associated With Progression to Chagas Disease Cardiomyopathy (vol 11, 1386, 2020)(2020) FRADE-BARROS, Amanda Farage; IANNI, Barbara Maria; CABANTOUS, Sandrine; PISSETTI, Cristina Wide; SABA, Bruno; LIN-WANG, Hui Tzu; BUCK, Paula; MARIN-NETO, Jose Antonio; SCHMIDT, Andre; DIAS, Fabricio; HIRATA, Mario Hiroyuki; SAMPAIO, Marcelo; FRAGATA, Abilio; PEREIRA, Alexandre Costa; DONADI, Eduardo; RODRIGUES, Virmondes; KALIL, Jorge; CHEVILLARD, Christophe; CUNHA-NETO, Edecio
- Blood DNA methylation marks discriminate Chagas cardiomyopathy disease clinical forms(2022) BROCHET, Pauline; IANNI, Barbara; NUNES, Joao P. S.; FRADE, Amanda F.; TEIXEIRA, Priscila C.; MADY, Charles; FERREIRA, Ludmila R. P.; KURAMOTO, Andreia; PISSETTI, Cristina W.; SABA, Bruno; CANDIDO, Darlan D. S.; DIAS, Fabricio; SAMPAIO, Marcelo; MARIN-NETO, Jose A.; FRAGATA, Abilio; ZANIRATTO, Ricardo C. F.; SIQUEIRA, Sergio; PEIXOTO, Giselle D. L.; RIGAUD, Vagner O. C.; BUCK, Paula; ALMEIDA, Rafael R.; LIN-WANG, Hui Tzu; SCHMIDT, Andre; MARTINELLI, Martino; HIRATA, Mario H.; DONADI, Eduardo; JUNIOR, Virmondes Rodrigues; PEREIRA, Alexandre C.; KALIL, Jorge; SPINELLI, Lionel; CUNHA-NETO, Edecio; CHEVILLARD, ChristopheChagas disease is a parasitic disease from South America, affecting around 7 million people worldwide. Decades after the infection, 30% of people develop chronic forms, including Chronic Chagas Cardiomyopathy (CCC), for which no treatment exists. Two stages characterized this form: the moderate form, characterized by a heart ejection fraction (EF) >= 0.4, and the severe form, associated to an EF < 0.4. We propose two sets of DNA methylation biomarkers which can predict in blood CCC occurrence, and CCC stage. This analysis, based on machine learning algorithms, makes predictions with more than 95% accuracy in a test cohort. Beyond their predictive capacity, these CpGs are located near genes involved in the immune response, the nervous system, ion transport or ATP synthesis, pathways known to be deregulated in CCCs. Among these genes, some are also differentially expressed in heart tissues. Interestingly, the CpGs of interest are tagged to genes mainly involved in nervous and ionic processes. Given the close link between methylation and gene expression, these lists of CpGs promise to be not only good biomarkers, but also good indicators of key elements in the development of this pathology.