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Previous studies indicated that<jats:named-content content-type=\"genus-species\">C. gattii<\/jats:named-content>strain R265 isolated from the Canadian outbreak had immune avoidance or immune suppression capabilities. However, protective immunity against<jats:named-content content-type=\"genus-species\">C. gattii<\/jats:named-content>has not been identified. In this study, we used a gain-of-function approach to investigate the protective immunity against<jats:named-content content-type=\"genus-species\">C. gattii<\/jats:named-content>infection using a dendritic cell (DC)-based vaccine. Bone marrow-derived dendritic cells (BMDCs) efficiently engulfed acapsular<jats:named-content content-type=\"genus-species\">C. gattii<\/jats:named-content>(\u0394<jats:italic>cap60<\/jats:italic>strain), which resulted in their expression of costimulatory molecules and inflammatory cytokines. This was not observed for BMDCs that were cultured with encapsulated strains. When \u0394<jats:italic>cap60<\/jats:italic>strain-pulsed BMDCs were transferred to mice prior to intratracheal R265 infection, significant amelioration of pathology, fungal burden, and the survival rate resulted compared with those in controls. Multinucleated giant cells (MGCs) that engulfed fungal cells were significantly increased in the lungs of immunized mice. Interleukin 17A (IL-17A)-, gamma interferon (IFN-\u03b3)-, and tumor necrosis factor alpha (TNF-\u03b1)-producing lymphocytes were significantly increased in the spleens and lungs of immunized mice. The protective effect of this DC vaccine was significantly reduced in IFN-\u03b3 knockout mice. These results demonstrated that an increase in cytokine-producing lymphocytes and the development of MGCs that engulfed fungal cells were associated with the protection against pulmonary infection with highly virulent<jats:named-content content-type=\"genus-species\">C. gattii<\/jats:named-content>and suggested that IFN-\u03b3 may have been an important mediator for this vaccine-induced protection.<\/jats:p>","DOI":"10.1128\/iai.02827-14","type":"journal-article","created":{"date-parts":[[2015,2,3]],"date-time":"2015-02-03T07:53:10Z","timestamp":1422949990000},"page":"1577-1586","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":32,"title":["Dendritic Cell-Based Immunization Ameliorates Pulmonary Infection with Highly Virulent Cryptococcus gattii"],"prefix":"10.1128","volume":"83","author":[{"given":"Keigo","family":"Ueno","sequence":"first","affiliation":[{"name":"Department of Chemotherapy and Mycoses, National 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