Dendritic cell-based systemic vaccination induces lung resident memory Th17 that contributes to long-term protection against pulmonary fungal infection

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K21644
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology; Bacteriology (including mycology)
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Ueno Keigo 国立感染症研究所, 真菌部, 主任研究官 (10550220)
• Research Collaborator: KINJO Yuki 国立感染症研究所, 真菌部3室, 室長 ; IWAKURA Yoichiro 東京理科大学, 生命医科学研究所, 教授 ; SHIBUYA Kazutoshi 東邦大学, 医学部・病院病理学講座, 教授 ; TAKATSUKA Yuki 国立感染症研究所, 真菌部3室, 研究員 ; ABE Masahiro 国立感染症研究所, 真菌部3室, 協力研究員 ; OTANI Yoshiko 国立感染症研究所, 真菌部3室, 実習生
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: Tissue Resident Memory / CD4+ Memory T cells / vaccine / fungal infection / Cryptococcus gattii / cytokine / granuloma

Outline of Final Research Achievements

We analyzed vaccine-mediated immunity using dendritic cell-based (DC) vaccine to elucidate the protective immunity against a fungal pathogen Cryptococcus gattii. In this study, we identified the novel lung resident memory Th17 cells (Lung TRM17) in the immunized mice, which has characteristic marker profiles and a long-lived trait. DC vaccine significantly ameliorated fungal burden and survival rate after infection, and it upregulated IL-17A production in lungs of immunized mice after infection. The protective effect of DC vaccine was significantly reduced in IL-17A deficient mice, but not in mice treated by the immunosuppressive agents FTY720. The infection control in the immunized mice was correlated with IL-17A dependent neutrophil activation and accumulation in the lungs after infection. These results suggested the Lung TRM17 contributed to the infection control against C. gattii in the vaccinated mice.

Free Research Field

感染免疫学