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One possibility is that the<jats:italic>L. amazonensis<\/jats:italic>parasite modulates antigen-presenting cells, favoring the generation of pathogenic Th cells that are capable of recruiting leukocytes but insufficient to fully activate their microbicidal activities. To test this possibility, we infected bone marrow-derived dendritic cells (DCs) of C57BL\/6 mice with<jats:italic>L. amazonensis<\/jats:italic>or<jats:italic>Leishmania major<\/jats:italic>promastigotes and assessed the activation of DC subsets and their capacity in priming CD4<jats:sup>+<\/jats:sup>T cells in vitro. In comparison to<jats:italic>L. major<\/jats:italic>controls,<jats:italic>L. amazonensis<\/jats:italic>-infected DCs secreted lower levels of interleukin-1\u03b1 (IL-1\u03b1) and IL-1\u03b2, were less potent in activating the IL-12p40-producing CD11c<jats:sup>high<\/jats:sup>CD45RB<jats:sup>\u2212<\/jats:sup>CD83<jats:sup>+<\/jats:sup>CD40<jats:sup>+<\/jats:sup>DC subset, and preferentially activated CD4<jats:sup>+<\/jats:sup>T cells with a IFN-\u03b3<jats:sup>low<\/jats:sup>IL-10<jats:sup>high<\/jats:sup>IL-17<jats:sup>high<\/jats:sup>phenotype. Although the addition of IL-1\u03b2 at the time of infection markedly enhanced DC activation and T-cell priming, it did not skew the cytokine profile of DCs and pathogenic Th cells, as local injection of IL-1\u03b2 following<jats:italic>L. amazonensis<\/jats:italic>infection accelerated Th cell activation and disease progression. This study suggests that intrinsic defects at the level of DC activation are responsible for the susceptible phenotype in<jats:italic>L. amazonensis<\/jats:italic>-infected hosts and that this parasite may have evolved unique mechanisms to interfere with innate and adaptive immunity.<\/jats:p>","DOI":"10.1128\/iai.00499-07","type":"journal-article","created":{"date-parts":[[2007,8,7]],"date-time":"2007-08-07T00:54:18Z","timestamp":1186448058000},"page":"5018-5026","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":62,"title":["Role of Interleukin-1\u03b2 in Activating the CD11c<sup>high<\/sup>CD45RB<sup>\u2212<\/sup>Dendritic Cell Subset and Priming<i>Leishmania amazonensis<\/i>- Specific CD4<sup>+<\/sup>T Cells In Vitro and In Vivo"],"prefix":"10.1128","volume":"75","author":[{"given":"Lijun","family":"Xin","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongguo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology"},{"name":"Department of Infectious Diseases, Harbin Medical University, Harbin, Hei Long Jiang Province, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn","family":"Soong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology"},{"name":"Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, Sealy Center for Vaccine Development, Institute for Human Infections and Immunity, University of Texas Medical Branch Galveston, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.7.2952-2959.1993"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061886"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.767"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04753"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.176.3.713"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.3.1416"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.2.457-461.1994"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.2.233"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-10-4190"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115611"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1254"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1648"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"4347","DOI":"10.4049\/jimmunol.155.9.4347","volume":"155","year":"1995","unstructured":"Hunter, C. 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