{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:34:18Z","timestamp":1791214458991,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2000,7,1]],"date-time":"2000-07-01T00:00:00Z","timestamp":962409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The aim of this study was to examine the contribution of IL-18 in host defense against infection caused by Cryptococcus neoformans in mice with defective IL-12 production. Experiments were conducted in mice with a targeted disruption of the gene for IL-12p40 subunit (IL-12p40\u2212\/\u2212 mice). In these mice, host resistance was impaired, as shown by increased number of organisms in both lungs and brains, compared with control mice. Serum IFN-\u03b3 was still detected in these mice at a considerable level (20\u201330% of that in control mice). The host resistance was moderately impaired in IL-12p40\u2212\/\u2212 mice compared with IFN-\u03b3\u2212\/\u2212 mice. Neutralizing anti-IFN-\u03b3 mAb further increased the lung burdens of organisms. In addition, treatment with neutralizing anti-IL-18 Ab almost completely abrogated the production of IFN-\u03b3 and also impaired the host resistance. Host resistance in IL-12p40\u2212\/\u2212 IL-18\u2212\/\u2212 mice was more profoundly impaired than in IL-12p40\u2212\/\u2212 mice. Administration of IL-12 as well as IL-18 increased the serum levels of IFN-\u03b3 and significantly restored the reduced host resistance. Spleen cells obtained from infected IL-12p40\u2212\/\u2212 mice did not produce any IFN-\u03b3 upon restimulation with the same organisms, while those from infected and IL-12-treated mice produced IFN-\u03b3. In contrast, IL-18 did not show such effect. Finally, depletion of NK cells by anti-asialo GM1 Ab mostly abrogated the residual production of IFN-\u03b3 in IL-12p40\u2212\/\u2212 mice. Our results indicate that IL-18 contributes to host resistance to cryptococcal infection through the induction of IFN-\u03b3 production by NK cells, but not through the development of Th1 cells, under the condition in which IL-12 synthesis is deficient.<\/jats:p>","DOI":"10.4049\/jimmunol.165.2.941","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T23:02:33Z","timestamp":1398121353000},"page":"941-947","source":"Crossref","is-referenced-by-count":111,"title":["IL-18 Contributes to Host Resistance Against Infection with\n                    <i>Cryptococcus neoformans<\/i>\n                    in Mice with Defective IL-12 Synthesis Through Induction of IFN-\u03b3 Production by NK Cells"],"prefix":"10.1093","volume":"165","author":[{"given":"Kazuyoshi","family":"Kawakami","sequence":"first","affiliation":[{"name":"First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus , Okinawa ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinobu","family":"Koguchi","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus , Okinawa ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahboob Hossain","family":"Qureshi","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus , Okinawa ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Miyazato","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus , Okinawa ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satomi","family":"Yara","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus , Okinawa ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kinjo","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus , Okinawa ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Iwakura","sequence":"additional","affiliation":[{"name":"Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Host Defense, Research Institute for Microbial Diseases, Osaka University , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuo","family":"Akira","sequence":"additional","affiliation":[{"name":"Department of Host Defense, Research Institute for Microbial Diseases, Osaka University , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Kurimoto","sequence":"additional","affiliation":[{"name":"Fujisaki Institute, Hayashibara Biochemical Laboratories , Okayama ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Saito","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus , Okinawa ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,7,15]]},"reference":[{"key":"2026020213064869500_R1","first-page":"11","volume-title":"Br. J. Clin. Practice","year":"1990"},{"key":"2026020213064869500_R2","first-page":"2331","volume-title":"Cryptococcus neoformans","year":"1995"},{"key":"2026020213064869500_R3","first-page":"5","volume-title":"Infect. Immun.","year":"1980"},{"key":"2026020213064869500_R4","first-page":"1472","volume-title":"J. Immunol.","year":"1990"},{"key":"2026020213064869500_R5","first-page":"793","volume-title":"J. Exp. Med.","year":"1991"},{"key":"2026020213064869500_R6","first-page":"755","volume-title":"J. Exp. Med.","year":"1991"},{"key":"2026020213064869500_R7","first-page":"35","volume-title":"J. Leukocyte Biol.","year":"1994"},{"key":"2026020213064869500_R8","first-page":"1129","volume-title":"J. Clin. Invest.","year":"1988"},{"key":"2026020213064869500_R9","first-page":"436","volume-title":"Clin. Exp. Immunol.","year":"1996"},{"key":"2026020213064869500_R10","first-page":"138","volume-title":"Immunol. Today","year":"1996"},{"key":"2026020213064869500_R11","first-page":"547","volume-title":"Science","year":"1993"},{"key":"2026020213064869500_R12","first-page":"2533","volume-title":"J. Immunol.","year":"1994"},{"key":"2026020213064869500_R13","first-page":"1883","volume-title":"J. Immunol.","year":"1994"},{"key":"2026020213064869500_R14","first-page":"5167","volume-title":"J. Immunol.","year":"1994"},{"key":"2026020213064869500_R15","first-page":"1553","volume-title":"Eur. J. Immunol.","year":"1996"},{"key":"2026020213064869500_R16","first-page":"39","volume-title":"J. Exp. Med.","year":"1997"},{"key":"2026020213064869500_R17","first-page":"4994","volume-title":"Infect. Immun.","year":"1998"},{"key":"2026020213064869500_R18","first-page":"460","volume-title":"Antimicrob. Agents Chemother.","year":"1994"},{"key":"2026020213064869500_R19","first-page":"208","volume-title":"Clin. Exp. Immunol.","year":"1996"},{"key":"2026020213064869500_R20","first-page":"1307","volume-title":"Infect. Immun.","year":"1997"},{"key":"2026020213064869500_R21","first-page":"88","volume-title":"Nature","year":"1995"},{"key":"2026020213064869500_R22","first-page":"571","volume-title":"Immunity.","year":"1997"},{"key":"2026020213064869500_R23","first-page":"299","volume-title":"J. Immunol.","year":"1998"},{"key":"2026020213064869500_R24","first-page":"478","volume-title":"Infect. Immun.","year":"1999"},{"key":"2026020213064869500_R25","first-page":"2401","volume-title":"J. Virol.","year":"1999"},{"key":"2026020213064869500_R26","first-page":"2821","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020213064869500_R27","first-page":"5528","volume-title":"J. Immunol.","year":"1997"},{"key":"2026020213064869500_R28","first-page":"3594","volume-title":"Infect. Immun.","year":"1997"},{"key":"2026020213064869500_R29","first-page":"643","volume-title":"Eur. J. Immunol.","year":"1999"},{"key":"2026020213064869500_R30","first-page":"1418","volume-title":"J. Immunol.","year":"1997"},{"key":"2026020213064869500_R31","first-page":"383","volume-title":"Immunity","year":"1998"},{"key":"2026020213064869500_R32","first-page":"851","volume-title":"Microbiol. Immunol.","year":"1994"},{"key":"2026020213064869500_R33","first-page":"230","volume-title":"Clin. Exp. Immunol.","year":"1994"},{"key":"2026020213064869500_R34","first-page":"827","volume-title":"J. Exp. Med.","year":"1989"},{"key":"2026020213064869500_R35","first-page":"2818","volume-title":"Infect. Immun.","year":"1994"},{"key":"2026020213064869500_R36","first-page":"5832","volume-title":"J. Immunol.","year":"1995"},{"key":"2026020213064869500_R37","first-page":"471","volume-title":"Immunity","year":"1996"},{"key":"2026020213064869500_R38","first-page":"3948","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1997"},{"key":"2026020213064869500_R39","first-page":"2103","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2026020213064869500_R40","first-page":"281","volume-title":"Adv. Immunol.","year":"1998"},{"key":"2026020213064869500_R41","first-page":"11","volume-title":"J. Allergy Clin. Immunol.","year":"1999"},{"key":"2026020213064869500_R42","first-page":"3231","volume-title":"Eur. J. Immunol.","year":"1998"},{"key":"2026020213064869500_R43","first-page":"2892","volume-title":"Infect. Immun.","year":"1991"},{"key":"2026020213064869500_R44","first-page":"2237","volume-title":"Eur. J. Immunol.","year":"1993"},{"key":"2026020213064869500_R45","first-page":"567","volume-title":"J. Exp. Med.","year":"1993"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/165\/2\/941\/62130021\/941.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/165\/2\/941\/62130021\/941.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T18:10:19Z","timestamp":1770055819000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/165\/2\/941\/8038340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,7]]},"references-count":45,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2000,7,15]]},"published-print":{"date-parts":[[2000,7,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.165.2.941","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2000,7]]},"published":{"date-parts":[[2000,7]]}}}