{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T20:08:27Z","timestamp":1788984507161,"version":"build-2803163510"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Doen\u00e7as Tropicais"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01AI138230-04"],"award-info":[{"award-number":["5R01AI138230-04"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Human infection with Trypanosoma cruzi leads to Chagas disease, which induces profound changes in the immune response across different cell subsets, influencing parasite control and disease pathology. Dissecting the functional characteristics of distinct immune cells in patients with the asymptomatic (indeterminate, IND) or the cardiac (CCC) clinical forms is crucial for unveiling mechanisms of disease progression and pathology, and identifying disease markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Immune-gene targeted single-cell RNA sequencing was applied to peripheral blood mononuclear cells obtained from patients with IND and CCC to unravel the immune landscape in these polar, well-characterized, clinical groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings revealed different myeloid and lymphoid cell clusters in the cohorts, each exhibiting unique gene expression patterns. CCC was characterized by an increased frequency of KLRB1+CD4+, TBX21+CD8+ T cells, and NK cells, which exhibited upregulation of genes associated with cytotoxic and apoptotic responses. Furthermore, we observed monocyte, B-cell subsets, along with dendritic cells, expressing inflammatory and notably cytotoxic genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results reveal cell-specific changes in patients with CCC compared to IND chronic Chagas disease, highlighted by distinct gene expression patterns. These nuanced changes indicate an immune signature linked to the clinical forms of chronic Chagas disease, which provide information regarding disease pathology, indicating potential markers related to the disease progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf269","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T08:52:05Z","timestamp":1747817525000},"page":"1402-1412","source":"Crossref","is-referenced-by-count":6,"title":["Single-Cell Targeted Transcriptomics Reveals Subset-Specific Immune Signatures Differentiating Asymptomatic and Cardiac Patients With Chronic Chagas Disease"],"prefix":"10.1093","volume":"232","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1068-0156","authenticated-orcid":false,"given":"Thaiany G","family":"Souza-Silva","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio Biologia das Intera\u00e7\u00f5es Celulares, Departamento Morfologia, Instituto de Ci\u00eancias Biol\u00f3gicas , Belo Horizonte, Minas Gerais ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4759-6679","authenticated-orcid":false,"given":"Amanda","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Center for Research in Immuno-Oncology, Hospital Israelita Albert Einstein , S\u00e3o Paulo, S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia L P","family":"Morais","sequence":"additional","affiliation":[{"name":"Center for Research in Immuno-Oncology, Hospital Israelita Albert Einstein , S\u00e3o Paulo, S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Apost\u00f3lico","sequence":"additional","affiliation":[{"name":"Center for Research in Immuno-Oncology, Hospital Israelita Albert Einstein , S\u00e3o Paulo, S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Pantaleao","sequence":"additional","affiliation":[{"name":"Departamento Cl\u00ednica M\u00e9dica, Faculdade de Medicina, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f4nio","family":"Mutarelli","sequence":"additional","affiliation":[{"name":"Departamento Cl\u00ednica M\u00e9dica, Faculdade de Medicina, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana Silva","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Departamento Cl\u00ednica M\u00e9dica, Faculdade de Medicina, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8801-1828","authenticated-orcid":false,"given":"Maria do Carmo Pereira","family":"Nunes","sequence":"additional","affiliation":[{"name":"Departamento Cl\u00ednica M\u00e9dica, Faculdade de Medicina, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J","family":"Gollob","sequence":"additional","affiliation":[{"name":"Center for Research in Immuno-Oncology, Hospital Israelita Albert Einstein , S\u00e3o Paulo, S\u00e3o Paulo ,","place":["Brazil"]},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Doen\u00e7as Tropicais \u00a0 , Salvador, Bahia ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7586-9996","authenticated-orcid":false,"given":"Walderez O","family":"Dutra","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio Biologia das Intera\u00e7\u00f5es Celulares, Departamento Morfologia, Instituto de Ci\u00eancias Biol\u00f3gicas , Belo Horizonte, Minas Gerais ,","place":["Brazil"]},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Doen\u00e7as Tropicais \u00a0 , Salvador, Bahia ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"2026031304480946400_jiaf269-B1","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.amjmed.2020.05.022","article-title":"Chagas disease: epidemiology and barriers to treatment","volume":"133","author":"Mills","year":"2020","journal-title":"Am J Med"},{"key":"2026031304480946400_jiaf269-B2","volume-title":"Chagas disease","author":"Pan American Health Organization\/World Health Organization","year":"2020"},{"key":"2026031304480946400_jiaf269-B3","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.idc.2012.03.002","article-title":"American trypanosomiasis (Chagas disease)","volume":"26","author":"Rassi","year":"2012","journal-title":"Infect Dis Clin North Am"},{"key":"2026031304480946400_jiaf269-B4","first-page":"155","volume-title":"Noncommunicable disease country profiles","author":"World Health Organization","year":"2021"},{"key":"2026031304480946400_jiaf269-B5","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/pim.12107","article-title":"Immunoregulatory networks in human chagas disease","volume":"36","author":"Dutra","year":"2014","journal-title":"Parasite Immunol"},{"key":"2026031304480946400_jiaf269-B6","doi-asserted-by":"crossref","first-page":"683230","DOI":"10.1155\/2014\/683230","article-title":"Chagas disease cardiomyopathy: immunopathology and genetics","volume":"2014","author":"Cunha-Neto","year":"2014","journal-title":"Mediators Inflamm"},{"key":"2026031304480946400_jiaf269-B7","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3390\/pathogens12020171","article-title":"Cytokine networks as targets for preventing and controlling Chagas heart disease","volume":"12","author":"Koh","year":"2023","journal-title":"Pathogens"},{"key":"2026031304480946400_jiaf269-B8","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/1471-2334-12-123","article-title":"Blood leukocytes from benznidazole-treated indeterminate chagas disease patients display an overall type-1-modulated cytokine profile upon short-term in vitro stimulation with Trypanosoma cruzi antigens","volume":"24","author":"Sathler-Avelar","year":"2012","journal-title":"BMC Infect Dis"},{"key":"2026031304480946400_jiaf269-B9","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1128\/IAI.01931-06","article-title":"Trypanosoma cruzi infection induces differential modulation of costimulatory molecules and cytokines by monocytes and T cells from patients with indeterminate and cardiac Chagas\u2019 disease","volume":"75","author":"Souza","year":"2007","journal-title":"Infect Immun"},{"key":"2026031304480946400_jiaf269-B10","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1086\/381682","article-title":"Frequency of interferon-\u03b3-producing T cells specific for Trypanosoma cruzi inversely correlates with disease severity in chronic human Chagas disease","volume":"189","author":"Laucella","year":"2004","journal-title":"J Infect Dis"},{"key":"2026031304480946400_jiaf269-B11","doi-asserted-by":"crossref","first-page":"787423","DOI":"10.3389\/fcvm.2022.787423","article-title":"T-cell subpopulations exhibit distinct recruitment potential, immunoregulatory profile and functional characteristics in Chagas versus idiopathic dilated cardiomyopathies","volume":"9","author":"Neves","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"2026031304480946400_jiaf269-B12","doi-asserted-by":"crossref","first-page":"637","DOI":"10.4269\/ajtmh.1993.48.637","article-title":"Characterization of inflammatory infiltrates in chronic myocardial lesions: presence of tumor necrosis factor-\u03b1+ cells and dominance of gramzyme A+, CD8+ lymphocytes","volume":"48","author":"Reis","year":"1993","journal-title":"Am J Trop Med Hyg"},{"key":"2026031304480946400_jiaf269-B13","doi-asserted-by":"crossref","first-page":"367","DOI":"10.3389\/fimmu.2019.00367","article-title":"Activation of human CD11b+ B1 B-cells by Trypanosoma cruzi-derived proteins is associated with protective immune response in human Chagas disease","volume":"10","author":"Passos","year":"2019","journal-title":"Front Immunol"},{"key":"2026031304480946400_jiaf269-B14","doi-asserted-by":"crossref","first-page":"1338582","DOI":"10.3389\/fimmu.2024.1338582","article-title":"Correlation of blood-based immune molecules with cardiac gene expression profiles reveals insights into Chagas cardiomyopathy pathogenesis","volume":"15","author":"Souza-Silva","year":"2024","journal-title":"Front Immunol"},{"key":"2026031304480946400_jiaf269-B15","doi-asserted-by":"crossref","first-page":"e169","DOI":"10.1161\/CIR.0000000000000599","article-title":"Chagas cardiomyopathy: an update of current clinical knowledge and management: a scientific statement from the American Heart Association","volume":"138","author":"Nunes","year":"2018","journal-title":"Circulation"},{"key":"2026031304480946400_jiaf269-B16","volume-title":"BD Bioscience","author":"Becton","year":"2019"},{"key":"2026031304480946400_jiaf269-B17","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/978-1-0716-2756-3_2","article-title":"BD rhapsody single-cell analysis system workflow: from sample to multimodal single-cell sequencing data","volume":"2584","author":"Ulbrich","year":"2023","journal-title":"Single Cell Transcr Methods Protoc"},{"key":"2026031304480946400_jiaf269-B18","doi-asserted-by":"crossref","first-page":"993025","DOI":"10.3389\/fimmu.2022.993025","article-title":"Potential role of HTLV-1 Tax-specific cytotoxic T lymphocytes expressing a unique T-cell receptor to promote inflammation of the central nervous system in myelopathy associated with HTLV-1","volume":"13","author":"Tanaka","year":"2022","journal-title":"Front Immunol"},{"key":"2026031304480946400_jiaf269-B19","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1189\/jlb.0309187","article-title":"CCL2\/MCP-1 controls parasite burden, cell infiltration, and mononuclear activation during acute Trypanosoma cruzi infection","volume":"86","author":"Paiva","year":"2009","journal-title":"J Leukoc Biol"},{"key":"2026031304480946400_jiaf269-B20","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.micinf.2014.08.005","article-title":"Transcriptional regulation of CCL20 expression","volume":"16","author":"Zhao","year":"2014","journal-title":"Microbes Infect"},{"key":"2026031304480946400_jiaf269-B21","doi-asserted-by":"crossref","first-page":"e20222129","DOI":"10.1084\/jem.20222129","article-title":"CCL5-producing migratory dendritic cells guide CCR5+ monocytes into the draining lymph nodes","volume":"220","author":"Rawat","year":"2023","journal-title":"J Exp Med"},{"key":"2026031304480946400_jiaf269-B22","doi-asserted-by":"crossref","first-page":"4819","DOI":"10.1128\/IAI.67.9.4819-4826.1999","article-title":"\u03b2-Chemokines enhance parasite uptake and promote nitric oxide-dependent microbiostatic activity in murine inflammatory macrophages infected with Trypanosoma cruzi","volume":"67","author":"Aliberti","year":"1999","journal-title":"Infect Immun"},{"key":"2026031304480946400_jiaf269-B23","first-page":"55","article-title":"Molecular markers to clinical forms of Chagas disease","volume":"42","author":"Guedes","year":"2009","journal-title":"Rev Soc Bras Med Trop"},{"key":"2026031304480946400_jiaf269-B24","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1093\/emboj\/19.7.1476","article-title":"Highly purified glycosylphosphatidylinositols from Trypanosoma cruzi are potent proinflammatory agents","volume":"19","author":"Almeida","year":"2000","journal-title":"EMBO J"},{"key":"2026031304480946400_jiaf269-B25","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1182\/blood-2009-07-235382","article-title":"Granzyme B produced by human plasmacytoid dendritic cells suppresses T-cell expansion","volume":"115","author":"Jahrsd\u00f6rfer","year":"2010","journal-title":"Blood"},{"key":"2026031304480946400_jiaf269-B26","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1182\/blood-2012-02-410803","article-title":"Deletion of cognate CD8 T cells by immature dendritic cells: a novel role for perforin, granzyme A, TREM-1, and TLR7","volume":"120","author":"Zangi","year":"2012","journal-title":"Blood"},{"key":"2026031304480946400_jiaf269-B27","doi-asserted-by":"crossref","first-page":"4127","DOI":"10.1182\/blood.V124.21.4127.4127","article-title":"Granzyme B is a key regulator of plasmacytoid dendritic cell immunogenicity","volume":"124","author":"Jahrsd\u00f6rfer","year":"2014","journal-title":"Blood"},{"key":"2026031304480946400_jiaf269-B28","doi-asserted-by":"crossref","first-page":"12078","DOI":"10.1038\/s41598-017-12171-3","article-title":"Differential regulation of effector and regulatory T cell function by Blimp1","volume":"7","author":"Bankoti","year":"2017","journal-title":"Sci Rep"},{"key":"2026031304480946400_jiaf269-B29","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/s12967-023-04066-x","article-title":"Exploring the putative role of PRDM1 and PRDM2 transcripts as mediators of T lymphocyte activation","volume":"21","author":"Di Zazzo","year":"2023","journal-title":"J Transl Med"},{"key":"2026031304480946400_jiaf269-B30","doi-asserted-by":"crossref","first-page":"1268196","DOI":"10.3389\/fimmu.2023.1268196","article-title":"Blimp-1 signaling pathways in T lymphocytes is essential to control the Trypanosoma cruzi infection-induced inflammation","volume":"14","author":"Benevides","year":"2023","journal-title":"Front Immunol"},{"key":"2026031304480946400_jiaf269-B31","doi-asserted-by":"crossref","first-page":"e1867","DOI":"10.1371\/journal.pntd.0001867","article-title":"Myocardial chemokine expression and intensity of myocarditis in chagas cardiomyopathy are controlled by polymorphisms in CXCL9 and CXCL10","volume":"6","author":"Nogueira","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"key":"2026031304480946400_jiaf269-B32","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.micinf.2008.11.012","article-title":"Treatment of chronically Trypanosoma cruzi-infected mice with a CCR1\/CCR5 antagonist (met-RANTES) results in amelioration of cardiac tissue damage","volume":"11","author":"Medeiros","year":"2009","journal-title":"Microbes Infect"},{"key":"2026031304480946400_jiaf269-B33","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/ni.3773","article-title":"The transcription factor Runx3 guards cytotoxic CD8+ effector T cells against deviation towards follicular helper T cell lineage","volume":"18","author":"Shan","year":"2017","journal-title":"Nat Immunol"},{"key":"2026031304480946400_jiaf269-B34","doi-asserted-by":"crossref","first-page":"914326","DOI":"10.1155\/2014\/914326","article-title":"Myocardial gene expression of T-bet, GATA-3, ROR-\u03b3 T, FOXP3, and hallmark cytokines in chronic Chagas disease cardiomyopathy: an essentially unopposed T-type response","volume":"2014","author":"Nogueira","year":"2014","journal-title":"Mediators Inflamm"},{"key":"2026031304480946400_jiaf269-B35","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1111\/j.1365-2567.2009.03169.x","article-title":"T-bet-dependent regulation of CD8+ T-cell expansion during experimental Trypanosoma cruzi infection","volume":"128","author":"Cobb","year":"2009","journal-title":"Immunology"},{"key":"2026031304480946400_jiaf269-B36","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.celrep.2016.05.095","article-title":"NKp80 defines a critical step during human natural killer cell development","volume":"16","author":"Freud","year":"2016","journal-title":"Cell Rep"},{"key":"2026031304480946400_jiaf269-B37","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/1521-4141(200101)31:1<233::AID-IMMU233>3.0.CO;2-4","article-title":"Identification of NKp80, a novel triggering molecule expressed by human NK cells","volume":"31","author":"Vitale","year":"2001","journal-title":"Eur J Immunol"},{"key":"2026031304480946400_jiaf269-B38","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.coi.2008.03.003","article-title":"Cytokine-producing B lymphocytes\u2014key regulators of immunity","volume":"20","author":"Lund","year":"2008","journal-title":"Curr Opin Immunol"},{"key":"2026031304480946400_jiaf269-B39","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/nri3857","article-title":"Antibody-independent functions of B cells: a focus on cytokines","volume":"15","author":"Shen","year":"2015","journal-title":"Nat Rev Immunol"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiaf269\/63306582\/jiaf269.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/232\/6\/1402\/63306582\/jiaf269.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/232\/6\/1402\/63306582\/jiaf269.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:48:31Z","timestamp":1773391711000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/232\/6\/1402\/8142201"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,28]]},"references-count":39,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,5,28]]},"published-print":{"date-parts":[[2025,12,20]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiaf269","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,12,15]]},"published":{"date-parts":[[2025,5,28]]}}}