{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:37:02Z","timestamp":1773391022713,"version":"3.50.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"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":[[2013,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>A differential behavior among infected and bystander dendritic cells (DCs) has been explored in different infection models. We have analyzed both populations sorted on contact with visceral Leishmania infantum on a susceptible mice model evaluating the subsequent repercussions on adaptive immune response. Our results demonstrate a clear dichotomy between the immunomodulatory abilities of bystander and infected DCs. The bystander population presents increased levels of IL-12p40 and costimulatory molecules being capable to induce CD4+ T cell activation with immune protective capabilities. In contrast, infected DCs, which express lower costimulatory molecules and higher levels of IL-10, promote the development of Leishmania Ag-specific, nonprotective T-bet+IFN-\u03b3+IL-10+ CD4+ T cells with an effector phenotype. This specific polarization was found to be dependent on IL-12p70. Splenic infected DCs recovered from chronic infected animals are similarly capable to polarize ex vivo syngeneic naive CD4+ T cells toward a T-bet+IFN-\u03b3+IL-10+ phenotype. Further analysis revealed that only MHC class IIhigh\u2013infected DCs were responsible for this polarization. The adoptive transfer of such polarized CD4+ T cells facilitates visceral leishmaniasis in BALB\/c mice in a clear contrast with their counterpart generated with bystander DCs that significantly potentiate protection. Further, we demonstrated that CD4+ T cells primed by infected DCs in an IL-10 free system, thus deprived of T-bet+IFN-\u03b3+IL-10+ population, restore the immune response and reduce parasite load, supporting a deleterious role of IFN-\u03b3+IL-10+ T cells in the maintenance of infection. Overall, our results highlight novel subversion mechanisms by which nonprotective T-bet+IFN-\u03b3+IL-10+ T cells are associated with chronicity and prolonged parasite persistence.<\/jats:p>","DOI":"10.4049\/jimmunol.1203518","type":"journal-article","created":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T05:15:07Z","timestamp":1370063707000},"page":"262-273","source":"Crossref","is-referenced-by-count":35,"title":["<i>Leishmania<\/i>-Infected MHC Class IIhigh Dendritic Cells Polarize CD4+ T Cells toward a Nonprotective T-bet+ IFN-\u03b3+ IL-10+ Phenotype"],"prefix":"10.1093","volume":"191","author":[{"given":"Mariana","family":"Resende","sequence":"first","affiliation":[{"name":"Parasite Disease Group, Institute for Molecular and Cell Biology, University of Porto , 4150-180 Porto,","place":["Portugal"]}]},{"given":"Diana","family":"Moreira","sequence":"additional","affiliation":[{"name":"Parasite Disease Group, Institute for Molecular and Cell Biology, University of Porto , 4150-180 Porto,","place":["Portugal"]}]},{"given":"Jorge","family":"Augusto","sequence":"additional","affiliation":[{"name":"Parasite Disease Group, Institute for Molecular and Cell Biology, University of Porto , 4150-180 Porto,","place":["Portugal"]}]},{"given":"Joana","family":"Cunha","sequence":"additional","affiliation":[{"name":"Parasite Disease Group, Institute for Molecular and Cell Biology, University of Porto , 4150-180 Porto,","place":["Portugal"]},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar e Faculdade de Medicina, Universidade do Porto , 4050-313 Porto,","place":["Portugal"]}]},{"given":"Bruno","family":"Neves","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience and Cell Biology, Faculty of Pharmacy, Universidade de Coimbra , 3004-517 Coimbra,","place":["Portugal"]},{"name":"Departamento de Qu\u00edmica, Centro de Espectrometria de Massa, Qu\u00edmica Org\u00e2nica, Produtos Naturais e Agro-alimentares, Universidade de Aveiro , 3810-193 Aveiro,","place":["Portugal"]}]},{"given":"Maria Teresa","family":"Cruz","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience and Cell Biology, Faculty of Pharmacy, Universidade de Coimbra , 3004-517 Coimbra,","place":["Portugal"]}]},{"given":"J\u00e9r\u00f4me","family":"Estaquier","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique Formation de Recherche en Evolution 3235, Universit\u00e9 Paris Descartes , 75006 Paris,","place":["France"]},{"name":"Universit\u00e9 Laval, Centre de Recherche en Infectiologie , Qu\u00e9bec G1V 4G2,","place":["Canada"]}]},{"given":"Anabela","family":"Cordeiro-da-Silva","sequence":"additional","affiliation":[{"name":"Parasite Disease Group, Institute for Molecular and Cell Biology, University of Porto , 4150-180 Porto,","place":["Portugal"]},{"name":"Departamento de Ci\u00eancias Biol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade do Porto , 4050-313 Porto,","place":["Portugal"]}]},{"given":"Ricardo","family":"Silvestre","sequence":"additional","affiliation":[{"name":"Parasite Disease Group, Institute for Molecular and Cell Biology, University of Porto , 4150-180 Porto,","place":["Portugal"]}]}],"member":"286","published-online":{"date-parts":[[2013,7,1]]},"reference":[{"key":"2025032405014461400_r1","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/nrmicro2608","article-title":"Leishmaniasis: complexity at the host-pathogen interface","volume":"9","author":"Kaye","year":"2011","journal-title":"Nat. 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