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Immunol."],"abstract":"<jats:p>The interaction of the anti-beta1-adrenergic receptor autoantibodies (\u03b21ARAb) and the anti-muscarinic M2 receptor autoantibodies (M2RAb) with cardiac neurotransmitter receptors were identified in human chronic Chagas cardiomyopathy (CCC) related to the ECG and dysautonomia disturbances. Dogs are considered gold model to the study of <jats:italic>Trypanosoma cruzi<\/jats:italic> infection due the clinical similarities with CCC. This study aims to evaluate whether anti-\u03b21ARAb, anti-\u03b22ARAb, and anti-muscarinic M2RAb are generated in Beagle dogs infected by <jats:italic>T. cruzi<\/jats:italic> using Y and Berenice-78 strains of <jats:italic>T. cruzi.<\/jats:italic> Animals were infected with 4.0 x 10<jats:sup>3<\/jats:sup> bloodstream trypomastigotes\/kg of body weight and, after 25 months of infection, blood sample was collected, and serum stored at -80\u00b0C. Dog serum was treated by ammonium sulphate precipitation and the IgG antibodies isolated and added to the beating neonatal rats\u2019 cardiomyocytes. All <jats:italic>T. cruzi<\/jats:italic>-infected dogs developed agonistic \u03b21ARAb, \u03b22ARAb, and M2RAb. Animals infected by Berenice strain presented less \u03b22ARAb and M2RAb activities than dogs infected by Y strain of the parasite. In cardiomyocytes culture, the antibodies recognized an epitope on the second extracellular loop of the receptors which were similar to findings in human Chagas disease. There was no detection of antibody against G protein-coupled receptor in serum from uninfected dogs. In conclusion, both Y and Berenice-78 strains of <jats:italic>T. cruzi<\/jats:italic> induced dog antibodies, whose targets located in the second extracellular loop of the adrenergic and muscarinic receptors were similar to those observed in individuals with CCC. Therefore, our findings highlight dogs as a promisor model to investigate pathogenic roles of functional Ab against G-protein coupled receptors.<\/jats:p>","DOI":"10.3389\/fimmu.2022.926682","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T07:05:27Z","timestamp":1666681527000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Functional antibodies against G-protein coupled receptors in Beagle dogs infected with two different strains of Trypanosoma cruzi"],"prefix":"10.3389","volume":"13","author":[{"given":"Gerd","family":"Wallukat","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando Ant\u00f4nio","family":"Botoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manoel\u00a0Ot\u00e1vio\u00a0da Costa","family":"Rocha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vit\u00f3ria","family":"Louise","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre","family":"Talvani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,25]]},"reference":[{"key":"B1","unstructured":"Ending the neglect to attain the sustainable development goals: A road map for neglected tropical diseases 2021\u201320302021"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n901","article-title":"Chagas disease in non-endemic settings","volume":"373","author":"Elkheir","year":"2021","journal-title":"BMJ"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2012.109","article-title":"Diagnosis and management of chagas disease and cardiomyopathy","volume":"9","author":"Ribeiro","year":"2012","journal-title":"Nat Rev Cardiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.627265","article-title":"Predictors of mortality in chronic chagas disease","volume":"115","author":"Rassi","year":"2007","journal-title":"Circulation"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1590\/0074-02760210172","article-title":"Prognosis of chronic chagas heart disease and other pending clinical challenges","volume":"116","author":"Torres","year":"2022","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1590\/s0074-02761999000700043","article-title":"Immunopathology of cardiomyopathy in the experimental chagas disease","volume":"94","author":"Soares","year":"1999","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"B7","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/s0008-6363(03)00361-4","article-title":"Pathophysiology of the heart in chagas' disease: current status and new developments","volume":"60","author":"Higuchi Mde","year":"2003","journal-title":"Cardiovasc Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01842","article-title":"Autoimmunity in chronic chagas disease: A road of multiple pathways to cardiomyopathy","volume":"9","author":"De Bona","year":"2018","journal-title":"Front Immunol"},{"key":"B9","article-title":"Pathology and pathological anatomy of chagas' disease","volume":"51","author":"Koberle","year":"1961","journal-title":"Bol Oficina Sanit Panam"},{"key":"B10","article-title":"A circulating IgG in chagas' disease which binds to beta-adrenoceptors of myocardium and modulates their activity","volume":"57","author":"Borda","year":"1984","journal-title":"Clin Exp Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.8.3541","article-title":"Autoimmunity in chagas disease cardiopathy: biological relevance of a cardiac myosin-specific epitope crossreactive to an immunodominant Trypanosoma cruzi antigen","volume":"92","author":"Cunha-Neto","year":"1995","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.01856","article-title":"Correlation of parasite burden, kDNA integration, autoreactive antibodies, and cytokine pattern in the pathophysiology of chagas disease","volume":"10","author":"Wesley","year":"2019","journal-title":"Front Microbiol"},{"key":"B13","article-title":"Antibodies to \u03b21 and \u03b22 adrenoceptor in chagas\u2019disease","volume":"74","author":"Sterin-Borda","year":"1988","journal-title":"Clin Exp Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.06.064","article-title":"Distinct patterns of autoantibodies against G-protein-coupled receptors in chagas' cardiomyopathy and megacolon. 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