{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:23:03Z","timestamp":1790518983117,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T00:00:00Z","timestamp":1558569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Visceral leishmaniasis, a chronic, potentially fatal disease, is characterized by high production of low\u2010affinity antibodies. In humans, hypergammaglobulinemia is prediction of disease progression. Nevertheless, the contribution of hypermutated and\/or class\u2010switched immunoglobulins to disease pathogenesis has never been studied. Using\n                    <jats:italic>\n                      Aicda\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice and the experimental model of\n                    <jats:italic>Leishmania donovani<\/jats:italic>\n                    infection, we demonstrate that the absence of hypermutated and\/or class\u2010switched antibodies was associated with increased resistance to disease, stronger protective Th1 responses, and a lower frequency of regulatory IFN\u03b3\n                    <jats:sup>+<\/jats:sup>\n                    IL\u201010\n                    <jats:sup>+<\/jats:sup>\n                    CD4 T\u00a0cells. Interestingly, stronger Th1 responses and the absence of IFN\u03b3\n                    <jats:sup>+<\/jats:sup>\n                    IL\u201010\n                    <jats:sup>+<\/jats:sup>\n                    CD4 T\u00a0cells during chronic infection in infected\n                    <jats:italic>\n                      Aicda\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice were not caused by a T\u2010cell intrinsic effect of AID, but by changes in the cytokine environment during chronic disease. Indeed TNF, IL\u201010 and IFN\u2010\u00df expressions were only upregulated in the presence of hypermutated, class\u2010switched antibodies and hypergammaglobulinemia at later stages of infection. Taken together, our results suggest that hypergammaglobulinemia sustains inhibitory responses during chronic visceral leishmaniasis.\n                  <\/jats:p>","DOI":"10.1002\/eji.201847917","type":"journal-article","created":{"date-parts":[[2019,4,19]],"date-time":"2019-04-19T01:38:40Z","timestamp":1555637920000},"page":"1082-1091","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Hypergammaglobulinemia sustains the development of regulatory responses during chronic\n                    <i>Leishmania donovani<\/i>\n                    infection in mice"],"prefix":"10.1002","volume":"49","author":[{"given":"Sasha","family":"Silva\u2010Barrios","sequence":"first","affiliation":[{"name":"INRS, Centre Armand\u2010Frappier Sant\u00e9 Biotechnologie  Laval Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5508-9565","authenticated-orcid":false,"given":"Simona","family":"St\u00e4ger","sequence":"additional","affiliation":[{"name":"INRS, Centre Armand\u2010Frappier Sant\u00e9 Biotechnologie  Laval Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/639304"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102880"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.7.3681"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2017.10.001"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939455"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.05.028"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.14-0260"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004096"},{"key":"e_1_2_7_10_1","doi-asserted-by":"crossref","first-page":"3813","DOI":"10.4049\/jimmunol.158.8.3813","article-title":"Destruction of follicular dendritic cells during chronic visceral leishmaniasis","volume":"158","author":"Smelt S. 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