{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:48:21Z","timestamp":1789447701988,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pntd.0014622","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000}}],"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01143496"],"award-info":[{"award-number":["R01143496"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007708","name":"Fondo Nacional de Ciencia Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PICT 2018\u201301522"],"award-info":[{"award-number":["PICT 2018\u201301522"]}],"id":[{"id":"10.13039\/501100007708","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ministerio de salud de la nacion Argentina"},{"name":"Ministerio de la Provincia de Buenos Aires Argentina"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Subjects with chronic Chagas disease and no signs of heart disease exhibit decreased NKp46 expression, high CD57 expression, and IL-10 production by NK cells. This study provides a detailed characterization of the phenotype and function of NK cells according to the severity of heart disease, and evaluates how these changes following treatment with benznidazole, as well as their association with\n                      <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                      -specific T-cell responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The phenotype and function of NK cells in a cohort of 51 subjects infected with\n                      <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                      and exhibiting varying degrees of heart disease were evaluated using high-dimensional flow cytometry and Boolean gating analysis. ELISPOT assays were performed to measure IFN-\u03b3 and IL-2 production in response to\n                      <jats:italic>T. cruzi<\/jats:italic>\n                      antigens, using CD56, CD4 and CD8-depleted PBMC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In contrast to individuals without heart disease, those with advanced cardiomyopathy have an increased number of NK cells that express the activating receptors NKp46 and CD16, as well as the differentiation marker CD57. NK cells in subjects with advanced cardiomyopathy were also found to be enriched in CD56\n                      <jats:sup>+<\/jats:sup>\n                      CD107\n                      <jats:sup>+<\/jats:sup>\n                      granzyme B\n                      <jats:sup>+<\/jats:sup>\n                      TNF-\u03b1\n                      <jats:sup>+<\/jats:sup>\n                      cells and depleted of CD56\n                      <jats:sup>+<\/jats:sup>\n                      IL-10\n                      <jats:sup>+<\/jats:sup>\n                      cells. The function of NK cells shifted towards monofunctionality in subjects with declining\n                      <jats:italic>T. cruzi<\/jats:italic>\n                      -specific antibodies following treatment with benznidazole. Eliminating CD56\n                      <jats:sup>+<\/jats:sup>\n                      cells significantly decreased the number of IFN-\u03b3-producing cells in response to\n                      <jats:italic>T. cruzi<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In chronic\n                      <jats:italic>T. cruzi<\/jats:italic>\n                      infection, NK-cell function may be balanced by the downregulation of activating receptors and IL-10 production, However, parasite persistence may desensitize the regulation of NK activating receptors, enabling NK cells to exert a potent polyfunctional cytotoxicity that potentially induce tissue damage.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0014622","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T17:46:30Z","timestamp":1786556790000},"page":"e0014622","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Natural killer (NK) cells with downregulated activating receptors and IL-10 production promote Trypanosoma cruzi T-cell responses in subjects in the Chronic phase of Trypanosoma cruzi infection: An exploratory immunological analysis"],"prefix":"10.1371","volume":"20","author":[{"given":"Mar\u00eda J.","family":"Elias","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonzalo","family":"Cesar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda G.","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel","family":"Podhorzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda B.","family":"Caputo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanza","family":"Lopez Albizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1ximo","family":"Carrega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio A.","family":"Tom\u00e1n Conte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda A.","family":"Natale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda C.","family":"Albareda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Lococo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5224-5446","authenticated-orcid":true,"given":"Susana A.","family":"Laucella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"pntd.0014622.ref001","doi-asserted-by":"crossref","DOI":"10.7326\/AITC202302210","article-title":"Chagas disease","volume":"176","author":"NS Hochberg","year":"2023","journal-title":"Ann Intern Med"},{"key":"pntd.0014622.ref002","unstructured":"World Health Organization. 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