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Here, we report that the PKC\u03b4 isoform regulates IL\u201012p40\/p70 production in macrophages and DC and that PKC\u03b4 deficiency in mice transforms the 129\/Sv healer to a non\u2010healer strain during cutaneous leishmaniasis. <jats:italic>Leishmania major<\/jats:italic>\u2010infected PKC\u03b4<jats:sup>\u2212\/\u2212<\/jats:sup> 129\/Sv mice developed a rapid increase in footpad swelling and parasite burden with disease progression, leading to necrosis and ulceration similar to non\u2010healer BALB\/c mice. Moreover, PKC\u03b4<jats:sup>\u2212\/\u2212<\/jats:sup> mice failed to develop delayed\u2010type hypersensitivity responses against <jats:italic>Leishmania<\/jats:italic> antigen. PKC\u03b4<jats:sup>\u2212\/\u2212<\/jats:sup> macrophages were fully functional with normal MHC class II surface expression and GM\u2010CSF production, recruitment to the draining lymph node and killing effector functions by NO production. In contrast, macrophages and DC produced significantly reduced IL\u201012p40 and IL\u201012p70 compared to the WT cells. Decreased IL\u201012 production resulted in diminished Th1 differentiation, as determined by a striking reduction in IFN\u2010\u03b3 by antigen\u2010specific stimulated CD4<jats:sup>+<\/jats:sup> T cells isolated from popliteal lymph nodes of <jats:italic>L. major<\/jats:italic>\u2010infected PKC\u03b4<jats:sup>\u2212\/\u2212<\/jats:sup> mice, explaining the \u201cnon\u2010healer\u201d phenotype. We conclude from these data that PKC\u03b4 is a regulator of IL\u201012p40\/p70 production by DC and macrophages, driving the healer phenotype during cutaneous leishmaniasis.<\/jats:p>","DOI":"10.1002\/eji.201040985","type":"journal-article","created":{"date-parts":[[2011,1,4]],"date-time":"2011-01-04T11:06:40Z","timestamp":1294139200000},"page":"706-715","source":"Crossref","is-referenced-by-count":23,"title":["PKC\u03b4 regulates IL\u201012p40\/p70 production by macrophages and dendritic cells, driving a type 1 healer phenotype in cutaneous leishmaniasis"],"prefix":"10.1002","volume":"41","author":[{"given":"Reto","family":"Guler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Afshar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berenice","family":"Arendse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suraj P.","family":"Parihar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Revaz\u2010Breton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Leitges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Schwegmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Brombacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,2]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20040704"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj20031406"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxm034"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.4.1795-1799.1998"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2004.08.011"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.12.3970-3980.2002"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200112902"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/416860a"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/416865a"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060381"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0105010"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0805438"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703496104"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2004.07.018"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.2.447"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.2.515"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(03)00067-X"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80460-4"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830260722"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.4.1367"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2007.09.004"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2008.04.011"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2006.05.025"},{"key":"e_1_2_6_25_2","doi-asserted-by":"crossref","first-page":"4794","DOI":"10.4049\/jimmunol.144.12.4794","article-title":"Macrophage killing of Leishmania parasite in vivo is mediated by nitric oxide from L\u2010arginine","volume":"144","author":"Liew F. 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