Vaccination with O-linked Mannans Protects against Systemic Candidiasis through Innate Lymphocyte Populations

Area of Science:

• Mycology
• Immunology
• Vaccinology

Background:

• Candida spp. are a leading cause of hospital-acquired infections and invasive fungal disease.
• Current vaccines against fungal pathogens are unavailable.
• Blastomyces Dectin-2 ligand endoglucanase 2 (Eng2) has shown vaccine potential against Blastomyces and adjuvant properties for other pathogens.

Purpose of the Study:

• To investigate if O-mannans from Blastomyces Eng2 alone can confer protection against Candida infections.
• To elucidate the mechanisms underlying O-mannan-mediated protection.

Main Methods:

• Systemic candidiasis model in mice.
• Assessment of fungal load, survival rates, and immune cell populations.
• Dectin-2 dependency studies.
• Analysis of innate lymphocyte activation and reactive oxygen species production.

Main Results:

• Blastomyces O-mannans alone significantly reduced kidney fungal burden and increased survival in a Dectin-2-dependent manner.
• Protection was mediated by innate lymphocyte populations, including TCR-γδ+ T cells, innate lymphoid cells, and NK cells.
• These cells subsequently activated neutrophils and monocytes to release reactive oxygen species.

Conclusions:

• Blastomyces O-mannan can induce long-term protection against systemic candidiasis independently of antigenic peptides.
• This protection is mediated by Dectin-2 and involves a trained immunity response orchestrated by innate lymphocytes.
• These findings suggest a novel glycan-based vaccine strategy for invasive fungal infections.