{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T15:47:47Z","timestamp":1778600867148,"version":"3.51.4"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Increasing evidence demonstrates that generation of extracellular adenosine from ATP, which is hydrolyzed by the CD39\/CD73 enzyme pair, attenuates the inflammatory response and deactivates macrophage antimicrobial mechanisms. Although CD73 is emerging as a critical pathway and therapeutic target in cardiovascular disorders, the involvement of this ectonucleotidase during myocardial infection has not been explored. Using a murine model of infection with Trypanosoma cruzi, the causal agent of Chagas cardiomyopathy, we observed a sudden switch from the classical M1 macrophage (microbicidal) phenotype toward an alternative M2 (repairing\/anti-inflammatory) phenotype that occurred within the myocardium very shortly after BALB\/c mice infection. The observed shift in M1\/M2 rate correlated with the cardiac cytokine milieu. Considering that parasite persistence within myocardium is a necessary and sufficient condition for the development of the chronic myocarditis, we hypothesized that CD73 activity may counteract cardiac macrophage microbicidal polarization, rendering the local immune response less effective. In fact, a transient treatment with a specific CD73 inhibitor (adenosine 5\u2032-\u03b1,\u03b2-methylene-diphosphate) enhanced the microbicidal M1 subset predominance, diminished IL-4\u2013 and IL-10\u2013producing CD4+ T cells, promoted a proinflammatory cytokine milieu, and reduced parasite load within the myocardium during the acute phase. As a direct consequence of these events, there was a reduction in serum levels of creatine kinase muscle\u2013brain isoenzyme, a myocardial-specific injury marker, and an improvement in the electrocardiographic characteristics during the chronic phase. Our results demonstrate that this purinergic system drives the myocardial immune response postinfection and harbors a promising potential as a therapeutic target.<\/jats:p>","DOI":"10.4049\/jimmunol.1600371","type":"journal-article","created":{"date-parts":[[2016,6,23]],"date-time":"2016-06-23T14:16:16Z","timestamp":1466691376000},"page":"814-823","source":"Crossref","is-referenced-by-count":37,"title":["CD73 Inhibition Shifts Cardiac Macrophage Polarization toward a Microbicidal Phenotype and Ameliorates the Outcome of Experimental Chagas Cardiomyopathy"],"prefix":"10.1093","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7052-5086","authenticated-orcid":false,"given":"Nicol\u00e1s Eric","family":"Ponce","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda\u2013Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Universidad Nacional de C\u00f3rdoba , C\u00f3rdoba 5000,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2075-8826","authenticated-orcid":false,"given":"Liliana Maria","family":"Sanmarco","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda\u2013Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Universidad Nacional de C\u00f3rdoba , C\u00f3rdoba 5000,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Eberhardt","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda\u2013Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Universidad Nacional de C\u00f3rdoba , C\u00f3rdoba 5000,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00f3nica Cristina","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Departamento de Farmacia, Facultad de Ciencias Qu\u00edmicas, Unidad de Investigaci\u00f3n y Desarrollo en Tecnolog\u00eda Farmac\u00e9utica\u2013Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Universidad Nacional de C\u00f3rdoba , C\u00f3rdoba 5000,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9ctor Walter","family":"Rivarola","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias M\u00e9dicas, Centro de Estudios e Investigaci\u00f3n de la Enfermedad de Chagas y Leishmaniasis, Universidad Nacional de C\u00f3rdoba , C\u00f3rdoba 5000,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roxana Carolina","family":"Cano","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda\u2013Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Universidad Nacional de C\u00f3rdoba , C\u00f3rdoba 5000,","place":["Argentina"]},{"name":"Facultad de Ciencias Qu\u00edmicas, UA \u00c1rea de Ciencias Agrarias, Ingenier\u00eda, Ciencias Biol\u00f3gicas y de la salud\u2013Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Universidad Cat\u00f3lica de C\u00f3rdoba , C\u00f3rdoba 5000,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6897-7702","authenticated-orcid":false,"given":"Maria Pilar","family":"Aoki","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda\u2013Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas, Universidad Nacional de C\u00f3rdoba , C\u00f3rdoba 5000,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,8,1]]},"reference":[{"key":"2025030617465719900_r1"},{"key":"2025030617465719900_r2","doi-asserted-by":"crossref","first-page":"510","DOI":"10.2174\/156652408785748004","article-title":"Chagas heart disease pathogenesis: one mechanism or many?","volume":"8","author":"Bonney","year":"2008","journal-title":"Curr. 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