{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T18:06:54Z","timestamp":1779214014870,"version":"3.51.4"},"reference-count":72,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases of the National Institutes of Health","award":["R01AI176457"],"award-info":[{"award-number":["R01AI176457"]}]},{"name":"The Swedish Foundation of International Cooperation in Research and Higher Education","award":["IB2020-8618"],"award-info":[{"award-number":["IB2020-8618"]}]},{"name":"Secretar\u00eda de Ciencia y Tecnolog\u00eda, Universidad Nacional de C\u00f3rdoba","award":["411\/18"],"award-info":[{"award-number":["411\/18"]}]},{"name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica (ANPCyT) Fondo para la Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","award":["PICT 2019-2085"],"award-info":[{"award-number":["PICT 2019-2085"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:p>\n                    Chagas disease, caused by\n                    <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                    , is endemic to Latin America and is characterized by chronic inflammation of cardiac tissues due to parasite persistence. Hypoxia within infected tissues may trigger the stabilization of HIF-1 and be linked to ATP release. Extracellular ATP exhibits microbicidal effects but is scavenged by CD39 and CD73 ectonucleotidases, which ultimately generate adenosine (ADO), a potent immunosuppressor. Here, we comprehensively study the importance of HIF-1 stabilization and the CD39\/CD73\/ADO axis, on CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells with the cytotoxic phenotype, in facilitating the persistence of\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    . Myocardial infection induces prominent areas of hypoxia, which is concomitant with HIF-1\u03b1 stabilization in T cells and linked to early expansion of CD39\n                    <jats:sup>+<\/jats:sup>\n                    CD73\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltrating population. Functional assays further demonstrate that HIF-1 stabilization and CD73 activity are associated with impaired CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell cytotoxic potential. RNA-Seq analysis reveals that HIF-1 and purinergic signaling pathways are overrepresented in cardiac tissues of patients with end-stage Chagas disease. The findings highlight a major effect of purinergic signaling on CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells with potential cytotoxic capacity in the setting of\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    infection and have translational implications for therapy.\n                  <\/jats:p>","DOI":"10.1172\/jci186785","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T14:00:34Z","timestamp":1751292034000},"source":"Crossref","is-referenced-by-count":6,"title":["Purinergic signaling modulates CD4+ T cells with cytotoxic potential during Trypanosoma cruzi infection"],"prefix":"10.1172","volume":"135","author":[{"given":"Gast\u00f3n","family":"Bergero","sequence":"first","affiliation":[{"name":"Universidad Nacional de C\u00f3rdoba, Facultad de Ciencias Qu\u00edmicas, Departamento de Bioqu\u00edmica Cl\u00ednica, C\u00f3rdoba, Argentina."},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Centro de Investigaci\u00f3n en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda (CIBICI), C\u00f3rdoba, Argentina."},{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet. Stockholm, Sweden."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanina L.","family":"Mazzocco","sequence":"additional","affiliation":[{"name":"Universidad Nacional de C\u00f3rdoba, Facultad de Ciencias Qu\u00edmicas, Departamento de Bioqu\u00edmica Cl\u00ednica, C\u00f3rdoba, Argentina."},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Centro de Investigaci\u00f3n en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda (CIBICI), C\u00f3rdoba, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Del Rosso","sequence":"additional","affiliation":[{"name":"Universidad Nacional de C\u00f3rdoba, Facultad de Ciencias Qu\u00edmicas, Departamento de Bioqu\u00edmica Cl\u00ednica, C\u00f3rdoba, Argentina."},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Centro de Investigaci\u00f3n en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda (CIBICI), C\u00f3rdoba, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruining","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet. Stockholm, Sweden."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zo\u00e9 M.","family":"Cejas Gallardo","sequence":"additional","affiliation":[{"name":"Universidad Nacional de C\u00f3rdoba, Facultad de Ciencias Qu\u00edmicas, Departamento de Bioqu\u00edmica Cl\u00ednica, C\u00f3rdoba, Argentina."},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Centro de Investigaci\u00f3n en Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda (CIBICI), C\u00f3rdoba, Argentina."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6374-0194","authenticated-orcid":true,"given":"Simon C.","family":"Robson","sequence":"additional","affiliation":[{"name":"Center for Inflammation Research, Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Rottenberg","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet. 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