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We used IL-12p40<jats:sup>\u2212\/\u2212<\/jats:sup>and IL-18<jats:sup>\u2212\/\u2212<\/jats:sup>mice to further investigate the role of IL-12 and IL-18 in control of<jats:italic>Salmonella enterica<\/jats:italic>serovar Typhimurium. While C57BL\/6 and IL-18<jats:sup>\u2212\/\u2212<\/jats:sup>mice were able to resolve attenuated<jats:italic>S. enterica<\/jats:italic>serovar Typhimurium infections, the IL-12p40<jats:sup>\u2212\/\u2212<\/jats:sup>mice succumbed to a high bacterial burden after 60 days. Using ovalbumin (OVA)-specific T-cell receptor transgenic T cells (OT-II cells), we demonstrated that following oral infection with recombinant<jats:italic>S. enterica<\/jats:italic>serovar Typhimurium expressing OVA, the OT-II cells proliferated in the mesenteric lymph nodes of C57BL\/6 and IL-18<jats:sup>\u2212\/\u2212<\/jats:sup>mice but not in IL-12p40<jats:sup>\u2212\/\u2212<\/jats:sup>mice. In addition, we demonstrated by flow cytometry that equivalent or increased numbers of T cells produced IFN-\u03b3 in IL-12p40<jats:sup>\u2212\/\u2212<\/jats:sup>mice compared with the numbers of T cells that produced IFN-\u03b3 in C57BL\/6 and IL-18<jats:sup>\u2212\/\u2212<\/jats:sup>mice. Finally, we demonstrated that removal of macrophages from<jats:italic>S. enterica<\/jats:italic>serovar Typhimurium-infected C57BL\/6 and IL-12p40<jats:sup>\u2212\/\u2212<\/jats:sup>mice did not affect the bacterial load, suggesting that impaired control of<jats:italic>S. enterica<\/jats:italic>serovar Typhimurium infection in the absence of IL-12p40 is not due to reduced macrophage bactericidal activities, while IL-18<jats:sup>\u2212\/\u2212<\/jats:sup>mice did rely on the presence of macrophages for control of the infection. Our results suggest that IL-12p40, but not IL-18, is critical to resolution of infections with attenuated<jats:italic>S. enterica<\/jats:italic>serovar Typhimurium and that especially the effects of IL-12p40 on proliferative responses of CD4<jats:sup>+<\/jats:sup>T cells, but not the ability of these cells to produce IFN-\u03b3, are important in the resolution of infection by this intracellular bacterial pathogen.<\/jats:p>","DOI":"10.1128\/iai.00971-07","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T00:49:23Z","timestamp":1190076563000},"page":"5753-5762","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Gamma Interferon-Independent Effects of Interleukin-12 on Immunity to<i>Salmonella enterica<\/i>Serovar Typhimurium"],"prefix":"10.1128","volume":"75","author":[{"given":"Jason D.","family":"Price","sequence":"first","affiliation":[{"name":"CRC for Vaccine Technology"},{"name":"Australian Bacterial Pathogenesis Program"},{"name":"Department of Microbiology &amp; Immunology, The University of Melbourne"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim R.","family":"Simpfendorfer","sequence":"additional","affiliation":[{"name":"CRC for Vaccine Technology"},{"name":"Australian Bacterial Pathogenesis Program"},{"name":"Department of Microbiology &amp; Immunology, The University of Melbourne"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radhakrishnam R.","family":"Mantena","sequence":"additional","affiliation":[{"name":"Australian Bacterial Pathogenesis Program"},{"name":"Department of Microbiology &amp; Immunology, The University of Melbourne"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Holden","sequence":"additional","affiliation":[{"name":"Australian Bacterial Pathogenesis Program"},{"name":"Department of Microbiology &amp; Immunology, The University of Melbourne"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Heath","sequence":"additional","affiliation":[{"name":"CRC for Vaccine Technology"},{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville VIC3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"van Rooijen","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, Vrije Universiteit VUMC, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Strugnell","sequence":"additional","affiliation":[{"name":"CRC for Vaccine Technology"},{"name":"Australian Bacterial Pathogenesis Program"},{"name":"Department of Microbiology &amp; Immunology, The University of Melbourne"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odilia L. 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