{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:28:45Z","timestamp":1790724525856,"version":"4.1.0"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T00:00:00Z","timestamp":1641340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI104531"],"award-info":[{"award-number":["R01AI104531"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM121595"],"award-info":[{"award-number":["R01GM121595"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA233945"],"award-info":[{"award-number":["R01CA233945"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                    infection induces a polyclonal B cell proliferative response characterized by maturation to plasma cells, excessive generation of germinal centers, and secretion of parasite-unrelated antibodies. Although traditionally reduced to the humoral response, several infectious and non-infectious models revealed that B lymphocytes could regulate and play crucial roles in cellular responses. Here, we analyze the trypomastigote-induced effect on B cells, their effects on CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and their correlation with\n                    <jats:italic>in vivo<\/jats:italic>\n                    findings. The trypomastigotes were able to induce the proliferation and the production of IL-10 or IL-6 of na\u00efve B cells in co-culture experiments. Also, we found that IL-10-producing B220\n                    <jats:sup>lo<\/jats:sup>\n                    cells were elicited\n                    <jats:italic>in vivo<\/jats:italic>\n                    . We also found up-regulated expression of FasL and PD-L1, proteins involved in apoptosis induction and inhibition of TCR signaling, and of BAFF and APRIL mRNAs, two B-cell growth factors. Interestingly, it was observed that IL-21, which plays a critical role in regulatory B cell differentiation, was significantly increased in B220\n                    <jats:sup>+<\/jats:sup>\n                    \/IL-21\n                    <jats:sup>+<\/jats:sup>\n                    in\n                    <jats:italic>in vivo<\/jats:italic>\n                    infections. This is striking since the secretion of IL-21 is associated with T helper follicular cells. Furthermore, trypomastigote-stimulated B-cell conditioned medium dramatically reduced the proliferation and increased the apoptotic rate on CD3\/CD28 activated CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, suggesting the development of effective regulatory B cells. In this condition, CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells showed a marked decrease in proliferation and viability with marginal IL-2 or IFN\u03b3 secretion, which is counterproductive with an efficient immune response against\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    . Altogether, our results show that B lymphocytes stimulated with trypomastigotes adopt a particular phenotype that exerts a strong regulation of this T cell compartment by inducing apoptosis, arresting cell division, and affecting the developing of a proinflammatory response.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2021.789373","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T02:40:09Z","timestamp":1641350409000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Trypanosoma cruzi Induces B Cells That Regulate the CD4+ T Cell Response"],"prefix":"10.3389","volume":"11","author":[{"given":"Mart\u00edn","family":"Somoza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Bertelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia A.","family":"Pratto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramiro E.","family":"Verdun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Campetella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Mucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01929","article-title":"The Unsolved Jigsaw Puzzle of the Immune Response in Chagas Disease","volume":"9","author":"Acevedo","year":"2018","journal-title":"Front. 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