{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["12"],"submitter":["Ferreira RR"],"pubmed_abstract":["Chronic Chagasic cardiomyopathy (CCC), a progressive inflammatory and fibrosing disease, is the most prominent clinical form of Chagas disease, a neglected tropical disease caused by <i>Trypanosoma cruzi</i> infection. During CCC, the parasite remains inside the cardiac cells, leading to tissue damage, involving extensive inflammatory response and irregular fibrosis. Among the fibrogenic factors is transforming growth factor-β (TGF-β), a key cytokine controlling extracellular matrix synthesis and degradation. TGF-β is involved in CCC onset and progression, with increased serum levels and activation of its signaling pathways in the cardiac tissue, which crucially contributes to fibrosis. Inhibition of the TGF-β signaling pathway attenuates <i>T. cruzi</i> infection and prevents cardiac damage in an experimental model of acute Chagas disease. The aim of this study was to investigate the effect of TGF-β neutralization on <i>T. cruzi</i> infection in both <i>in vitro</i> and <i>in vivo</i> pre-clinical models, using the 1D11 monoclonal antibody. To this end, primary cultures of cardiac cells were infected with <i>T. cruzi</i> trypomastigote forms and treated with 1D11. For <i>in vivo</i> studies, 1D11 was administered in different schemes for acute and chronic phase models (Swiss mice infected with 10<sup>4</sup> parasites from the Y strain and C57BL/6 mice infected with 10<sup>2</sup> parasites from the Colombian strain, respectively). Here we show that the addition of 1D11 to cardiac cells greatly reduces cardiomyocyte invasion by <i>T. cruzi</i> and the number of parasites per infected cell. In both acute and chronic experimental models, <i>T. cruzi</i> infection altered the electrical conduction, decreasing the heart rate, increasing the PR interval and the P wave duration. The treatment with 1D11 reduced cardiac fibrosis and reversed electrical abnormalities improving cardiac performance. Taken together, these data further support the major role of the TGF-β signaling pathways in <i>T. cruzi</i>-infection and their biological consequences on parasite/host interactions. The therapeutic effects of the 1D11 antibody are promising and suggest a new possibility to treat cardiac fibrosis in the chronic phase of Chagas' heart disease by TGF-β neutralization."],"journal":["Frontiers in cellular and infection microbiology"],"pagination":["1017040"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9748701"],"repository":["biostudies-literature"],"pubmed_title":["In Chagas disease, transforming growth factor beta neutralization reduces <i>Trypanosoma cruzi</i> infection and improves cardiac performance."],"pmcid":["PMC9748701"],"pubmed_authors":["Ferreira NVC","Lannes-Vieira J","de Araujo-Jorge TC","Barker RH","Waghabi MC","Vilar-Pereira G","Meuser-Batista M","Abreu RDS","Feige JJ","Ledbeter S","Ferreira RR","Bailly S","de Souza EM","Degrave WMS"],"additional_accession":[]},"is_claimable":false,"name":"In Chagas disease, transforming growth factor beta neutralization reduces <i>Trypanosoma cruzi</i> infection and improves cardiac performance.","description":"Chronic Chagasic cardiomyopathy (CCC), a progressive inflammatory and fibrosing disease, is the most prominent clinical form of Chagas disease, a neglected tropical disease caused by <i>Trypanosoma cruzi</i> infection. During CCC, the parasite remains inside the cardiac cells, leading to tissue damage, involving extensive inflammatory response and irregular fibrosis. Among the fibrogenic factors is transforming growth factor-β (TGF-β), a key cytokine controlling extracellular matrix synthesis and degradation. TGF-β is involved in CCC onset and progression, with increased serum levels and activation of its signaling pathways in the cardiac tissue, which crucially contributes to fibrosis. Inhibition of the TGF-β signaling pathway attenuates <i>T. cruzi</i> infection and prevents cardiac damage in an experimental model of acute Chagas disease. The aim of this study was to investigate the effect of TGF-β neutralization on <i>T. cruzi</i> infection in both <i>in vitro</i> and <i>in vivo</i> pre-clinical models, using the 1D11 monoclonal antibody. To this end, primary cultures of cardiac cells were infected with <i>T. cruzi</i> trypomastigote forms and treated with 1D11. For <i>in vivo</i> studies, 1D11 was administered in different schemes for acute and chronic phase models (Swiss mice infected with 10<sup>4</sup> parasites from the Y strain and C57BL/6 mice infected with 10<sup>2</sup> parasites from the Colombian strain, respectively). Here we show that the addition of 1D11 to cardiac cells greatly reduces cardiomyocyte invasion by <i>T. cruzi</i> and the number of parasites per infected cell. In both acute and chronic experimental models, <i>T. cruzi</i> infection altered the electrical conduction, decreasing the heart rate, increasing the PR interval and the P wave duration. The treatment with 1D11 reduced cardiac fibrosis and reversed electrical abnormalities improving cardiac performance. Taken together, these data further support the major role of the TGF-β signaling pathways in <i>T. cruzi</i>-infection and their biological consequences on parasite/host interactions. The therapeutic effects of the 1D11 antibody are promising and suggest a new possibility to treat cardiac fibrosis in the chronic phase of Chagas' heart disease by TGF-β neutralization.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022","modification":"2025-04-18T16:31:10.822Z","creation":"2025-04-07T03:46:17.698Z"},"accession":"S-EPMC9748701","cross_references":{"pubmed":["36530434"],"doi":["10.3389/fcimb.2022.1017040"]}}