Galectin-3 impacts Cryptococcus neoformans infection through direct antifungal effects

Fausto Almeida, Julie M. Wolf, Thiago Aparecido Da Silva, Carlos M. Deleon-Rodriguez, Caroline Patini Rezende, André Moreira Pessoni, Fabrício Freitas Fernandes, Rafael Silva-Rocha, Roberto Martinez, Marcio L. Rodrigues, Maria Cristina Roque-Barreira, Arturo Casadevall

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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.

Original languageEnglish (US)
Article number1968
JournalNature Communications
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Almeida, F., Wolf, J. M., Da Silva, T. A., Deleon-Rodriguez, C. M., Rezende, C. P., Pessoni, A. M., ... Casadevall, A. (2017). Galectin-3 impacts Cryptococcus neoformans infection through direct antifungal effects. Nature Communications, 8(1), [1968]. https://doi.org/10.1038/s41467-017-02126-7