Dendritic cell-based immunization ameliorates pulmonary infection with highly virulent Cryptococcus gattii

Area of Science:

• Immunology
• Mycology
• Vaccinology

Background:

• Cryptococcus gattii is a highly virulent fungus causing fatal infections, even in immunocompetent individuals.
• The C. gattii R265 strain exhibits immune evasion properties, and protective immunity remains unidentified.
• Dendritic cells (DCs) are crucial in initiating adaptive immune responses.

Purpose of the Study:

• To investigate protective immunity against C. gattii using a dendritic cell (DC)-based vaccine.
• To evaluate the efficacy of a vaccine composed of bone marrow-derived dendritic cells (BMDCs) pulsed with an acapsular C. gattii strain.

Main Methods:

• Bone marrow-derived dendritic cells (BMDCs) were cultured with acapsular (Δcap60) or encapsulated C. gattii strains.
• BMDCs pulsed with the Δcap60 strain were transferred to mice before intratracheal challenge with the virulent R265 strain.
• Immune responses, pathology, fungal burden, survival, and the role of gamma interferon (IFN-γ) were assessed.

Main Results:

• BMDCs efficiently engulfed the acapsular Δcap60 strain, upregulating costimulatory molecules and cytokines.
• Vaccination with Δcap60-pulsed BMDCs significantly reduced pathology, fungal burden, and improved survival in mice.
• Increased multinucleated giant cells (MGCs), and lymphocytes producing IL-17A, IFN-γ, and TNF-α were observed in vaccinated mice.
• The protective effect was diminished in IFN-γ knockout mice, highlighting IFN-γ's crucial role.

Conclusions:

• A dendritic cell (DC)-based vaccine using an acapsular C. gattii strain confers protection against pulmonary C. gattii infection.
• Protection is associated with enhanced cytokine production (including IFN-γ) and the formation of fungal-engulfing MGCs.
• IFN-γ is a key mediator of vaccine-induced protection against virulent C. gattii.