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Automated Measurement of Cryptococcal Species Polysaccharide Capsule and Cell Body
Published on: January 11, 2018
Galectin-3 impacts Cryptococcus neoformans infection through direct antifungal effects
Fausto Almeida1, Julie M Wolf2, Thiago Aparecido da Silva3
1Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, 14049-900, Brazil.
Abstract:
Cryptococcus neoformans is an encapsulated fungal pathogen that causes cryptococcosis, which is a major opportunistic infection in immunosuppressed individuals. Mammalian β-galactoside-binding protein Galectin-3 (Gal-3) modulates the host innate and adaptive immunity, and plays significant roles during microbial infections including some fungal diseases. Here we show that this protein plays a role also in C. neoformans infection. We find augmented Gal-3 serum levels in human and experimental infections, as well as in spleen, lung, and brain tissues of infected mice. Gal-3-deficient mice are more susceptible to cryptococcosis than WT animals, as demonstrated by the higher fungal burden and lower animal survival. In vitro experiments show that Gal-3 inhibits fungal growth and exerts a direct lytic effect on C. neoformans extracellular vesicles (EVs). Our results indicate a direct role for Gal-3 in antifungal immunity whereby this molecule affects the outcome of C. neoformans infection by inhibiting fungal growth and reducing EV stability, which in turn could benefit the host.
Insights
Galectin-3 (Gal-3) enhances immunity against Cryptococcus neoformans fungal infections. Gal-3 deficiency increases susceptibility, while Gal-3 inhibits fungal growth and destabilizes fungal extracellular vesicles, improving host outcomes.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Cryptococcus neoformans causes opportunistic infections in immunocompromised individuals.
- Galectin-3 (Gal-3) is a mammalian protein modulating host immunity during microbial infections.
Purpose of the Study:
- To investigate the role of Galectin-3 (Gal-3) in Cryptococcus neoformans infection.
- To determine Gal-3's impact on host immune response and fungal pathogenesis.
Main Methods:
- Measured Gal-3 serum and tissue levels in human and murine cryptococcosis models.
- Assessed cryptococcosis severity in Gal-3-deficient mice compared to wild-type.
- Performed in vitro studies on Gal-3's effect on C. neoformans growth and extracellular vesicles.
Main Results:
- Elevated Gal-3 levels observed in serum and tissues during C. neoformans infection.
- Gal-3-deficient mice exhibited increased fungal burden and reduced survival.
- In vitro, Gal-3 inhibited fungal growth and lysed C. neoformans extracellular vesicles.
Conclusions:
- Galectin-3 plays a direct role in antifungal immunity against C. neoformans.
- Gal-3 limits fungal growth and destabilizes extracellular vesicles, contributing to host protection.
