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The role of IL-12 and IL-23 in protection conferred by the tuberculosis vaccine<jats:italic>Mycobacterium bovis<\/jats:italic>bacillus Calmette-Gue\u0301rin (BCG) is, however, less well documented. By using an autovaccine approach, i.e., IL-12p70 cross-linked with ovalbumin and PADRE peptide formulated with the GSK proprietary adjuvant system AS02<jats:sub>V<\/jats:sub>, we could specifically neutralize IL-12 while leaving the IL-23 axis intact. Neutralization of IL-12 before<jats:italic>M. tuberculosis<\/jats:italic>challenge rendered C57BL\/6 mice highly susceptible, resulting in 30-fold-higher CFU in spleen and lungs and accelerated mortality. In contrast, neutralization of IL-12 in BCG-vaccinated mice prior to<jats:italic>M. tuberculosis<\/jats:italic>challenge only marginally affected vaccine-mediated protection. Analysis of cytokine production in spleen and lungs 3 weeks post-TB challenge by enzyme-linked immunosorbent assay and functional and flow cytometric assays showed significantly reduced mycobacterium-specific gamma interferon (IFN-\u03b3) responses in<jats:italic>M. tuberculosis<\/jats:italic>-infected and BCG-vaccinated mice that had been treated with the autovaccine. Purified protein derivative-induced tumor necrosis factor alpha (TNF-\u03b1), IL-6, and IL-17A levels, however, were highest in lungs from BCG-vaccinated\/IL-12-neutralized animals, and even unstimulated lung cells from these mice produced significant levels of the three cytokines. Mycobacterium-specific IL-4 and IL-5 production levels were overall very low, but IL-12 neutralization resulted in increased concanavalin A-triggered polyclonal secretion of these Th2-type cytokines. These results suggest that TNF-\u03b1, IL-6, and IL-17A may be more important pulmonary effector molecules of BCG-mediated protection than IFN-\u03b3 in a context of IL-12 deficiency.<\/jats:p>","DOI":"10.1128\/cvi.00352-10","type":"journal-article","created":{"date-parts":[[2010,11,18]],"date-time":"2010-11-18T03:25:38Z","timestamp":1290050738000},"page":"95-104","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Increased Pulmonary Tumor Necrosis Factor Alpha, Interleukin-6 (IL-6), and IL-17A Responses Compensate for Decreased Gamma Interferon Production in Anti-IL-12 Autovaccine-Treated,<i>Mycobacterium bovis<\/i>BCG-Vaccinated Mice"],"prefix":"10.1128","volume":"18","author":[{"given":"Danielle","family":"Freches","sequence":"first","affiliation":[{"name":"WIV-ISP Site Ukkel, 1180 Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research and Cellular Genetics Unit, Universite\u0301 Catholique de Louvain, Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research and Experimental Medicine Unit, Universite\u0301 Catholique de Louvain, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Romano","sequence":"additional","affiliation":[{"name":"WIV-ISP Site Ukkel, 1180 Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research and Cellular Genetics Unit, Universite\u0301 Catholique de Louvain, Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research and Experimental Medicine Unit, Universite\u0301 Catholique de Louvain, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannelie","family":"Korf","sequence":"additional","affiliation":[{"name":"WIV-ISP Site Ukkel, 1180 Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research and Cellular Genetics Unit, Universite\u0301 Catholique de Louvain, Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research and Experimental Medicine Unit, Universite\u0301 Catholique de Louvain, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Christophe","family":"Renauld","sequence":"additional","affiliation":[{"name":"WIV-ISP Site Ukkel, 1180 Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research and Cellular Genetics Unit, Universite\u0301 Catholique de Louvain, Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research and Experimental Medicine Unit, Universite\u0301 Catholique de Louvain, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Van Snick","sequence":"additional","affiliation":[{"name":"WIV-ISP Site Ukkel, 1180 Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research and Cellular Genetics Unit, Universite\u0301 Catholique de Louvain, Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research and Experimental Medicine Unit, Universite\u0301 Catholique de Louvain, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Uyttenhove","sequence":"additional","affiliation":[{"name":"WIV-ISP Site Ukkel, 1180 Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research and Cellular Genetics Unit, Universite\u0301 Catholique de Louvain, Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research and Experimental Medicine Unit, Universite\u0301 Catholique de Louvain, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kris","family":"Huygen","sequence":"additional","affiliation":[{"name":"WIV-ISP Site Ukkel, 1180 Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research and Cellular Genetics Unit, Universite\u0301 Catholique de Louvain, Brussels, Belgium"},{"name":"Ludwig Institute for Cancer Research and Experimental Medicine Unit, Universite\u0301 Catholique de Louvain, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1074\/jbc.M207577200","volume":"278","year":"2003","unstructured":"Aggarwal, S., N. 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