RRC ID 40092
Author Ueno K, Kinjo Y, Okubo Y, Aki K, Urai M, Kaneko Y, Shimizu K, Wang DN, Okawara A, Nara T, Ohkouchi K, Mizuguchi Y, Kawamoto S, Kamei K, Ohno H, Niki Y, Shibuya K, Miyazaki Y.
Title Dendritic cell-based immunization ameliorates pulmonary infection with highly virulent Cryptococcus gattii.
Journal Infect Immun
Abstract Cryptococcosis due to a highly virulent fungus, Cryptococcus gattii, emerged as an infectious disease on Vancouver Island in Canada and surrounding areas in 1999, causing deaths among immunocompetent individuals. Previous studies indicated that C. gattii strain R265 isolated from the Canadian outbreak had immune avoidance or immune suppression capabilities. However, protective immunity against C. gattii has not been identified. In this study, we used a gain-of-function approach to investigate the protective immunity against C. gattii infection using a dendritic cell (DC)-based vaccine. Bone marrow-derived dendritic cells (BMDCs) efficiently engulfed acapsular C. gattii (Δcap60 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 Δcap60 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-γ)-, and tumor necrosis factor alpha (TNF-α)-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-γ 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 C. gattii and suggested that IFN-γ may have been an important mediator for this vaccine-induced protection.
Volume 83(4)
Pages 1577-86
Published 2015-4
DOI 10.1128/IAI.02827-14
PII IAI.02827-14
PMID 25644007
PMC PMC4363414
MeSH Animals Bone Marrow Cells / immunology Cell- and Tissue-Based Therapy Cryptococcosis / immunology* Cryptococcosis / prevention & control Cryptococcus gattii / immunology* Dendritic Cells / immunology Dendritic Cells / transplantation* Fungal Capsules / genetics Fungal Capsules / immunology* Fungal Vaccines / immunology* Giant Cells / immunology Interferon-gamma / genetics Interferon-gamma / immunology Interleukin-17 / immunology Lung / immunology Lung / microbiology Lymphocytes / immunology Mice Mice, Inbred C57BL Mice, Knockout Tumor Necrosis Factor-alpha / immunology Vaccination
IF 3.16
Times Cited 11
Pathogenic microorganisms ?