{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T20:19:37Z","timestamp":1782245977103,"version":"3.54.5"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>IL-4 and IL-13 cytokines have been associated with a non-healing phenotype in murine leishmaniasis in<jats:italic>L. mexicana<\/jats:italic>-infected BALB\/c mice as demonstrated in IL-4<jats:sup>\u2212\/\u2212<\/jats:sup>, IL-13<jats:sup>\u2212\/\u2212<\/jats:sup>and IL-4R\u03b1<jats:sup>-\/-<\/jats:sup>global knockout mouse studies. However, it is unclear from the studies which cell-type-specific IL-4\/IL-13 signaling mediates protection to<jats:italic>L. mexicana<\/jats:italic>. Previous studies have ruled out a role for IL-4-mediated protection on CD4<jats:sup>+<\/jats:sup>T cells during<jats:italic>L. mexicana<\/jats:italic>infections. A candidate for this role may be non-lymphocyte cells, particularly DCs, as was previously shown in<jats:italic>L. major<\/jats:italic>infections, where IL-4 production drives dendritic cell-IL-12 production thereby mediating a type 1 immune response. However, it is unclear if this IL-4-instruction of type 1 immunity also occurs in CL caused by<jats:italic>L. mexicana<\/jats:italic>, since the outcome of cutaneous leishmaniasis often depends on the infecting<jats:italic>Leishmania<\/jats:italic>species. Thus, BALB\/c mice with cell-specific deletion of the IL-4R\u03b1 on CD11c<jats:sup>+<\/jats:sup>DCs (CD11c<jats:sup>cre<\/jats:sup>IL-4R\u03b1<jats:sup>-\/lox<\/jats:sup>) were infected with<jats:italic>L. mexicana<\/jats:italic>promastigotes in the footpad and the clinical phenotype, humoral and cellular immune responses were investigated, compared to the littermate control. Our results show that CL disease progression in BALB\/c mice is independent of IL-4R\u03b1 signaling on DCs as CD11c<jats:sup>cre<\/jats:sup>IL-4R\u03b1<jats:sup>-\/lox<\/jats:sup>mice had similar footpad lesion progression, parasite loads, humoral responses (IgE, IgG1, IgG 2a\/b), and IFN-\u03b3 cytokine secretion in comparison to littermate controls. Despite this comparable phenotype, surprisingly, IL-4 production in CD11c<jats:sup>cre<\/jats:sup>IL-4R\u03b1<jats:sup>-\/lox<\/jats:sup>mice was significantly increased with an increasing trend of IL-13 when compared to littermate controls. Moreover, the absence of IL-4R\u03b1 signaling did not significantly alter the frequency of CD4 and CD8 lymphocytes nor their activation, or memory phenotype compared to littermate controls. However, these populations were significantly increased in CD11c<jats:sup>cre<\/jats:sup>IL-4R\u03b1<jats:sup>-\/lox<\/jats:sup>mice due to greater total cell infiltration into the lymph node. A similar trend was observed for B cells whereas the recruitment of myeloid populations (macrophages, DCs, neutrophils, and Mo-DCs) into LN was comparable to littermate IL-4R\u03b1<jats:sup>-\/lox<\/jats:sup>mice. Interestingly, IL-4R\u03b1-deficient bone marrow-derived dendritic cells (BMDCs), stimulated with LPS or<jats:italic>L. mexicana<\/jats:italic>promastigotes in presence of IL-4, showed similar levels of IL-12p70 and IL-10 to littermate controls highlighting that IL-4-mediated DC instruction was not impaired in response to<jats:italic>L. mexicana<\/jats:italic>. Similarly, IL-4 stimulation did not affect the maturation or activation of IL-4R\u03b1-deficient BMDCs during<jats:italic>L. mexicana<\/jats:italic>infection nor their effector functions in production of nitrite and arginine-derived metabolite (urea). Together, this study suggests that IL-4 R\u03b1 signaling on DCs is not key in the regulation of immune-mediated protection in mice against<jats:italic>L. mexicana<\/jats:italic>infection.<\/jats:p>","DOI":"10.3389\/fimmu.2021.759021","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T07:02:39Z","timestamp":1643353359000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Interleukin-4 Responsive Dendritic Cells Are Dispensable to Host Resistance Against Leishmania mexicana Infection"],"prefix":"10.3389","volume":"12","author":[{"given":"Bernard Ong\u2019ondo","family":"Osero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zama","family":"Cele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael 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