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.
Highlights
Cryptococcus neoformans is an encapsulated fungal pathogen that causes cryptococcosis, which is a major opportunistic infection in immunosuppressed individuals
We compared the severity of the C. neoformans infection in Gal-3KO and WT mice, assessed the Gal-3 content in organs of infected mice, and determined the Gal-3 serum levels in both experimental and human cryptococcosis
Our results demonstrate that Gal-3 plays relevant roles in C. neoformans infection primarily through direct effects on cryptococcal cells and their products
Summary
Cryptococcus neoformans is an encapsulated fungal pathogen that causes cryptococcosis, which is a major opportunistic infection in immunosuppressed individuals. Mammalian βgalactoside-binding protein Galectin-3 (Gal-3) modulates the host innate and adaptive immunity, and plays significant roles during microbial infections including some fungal diseases. 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. The most important virulence factors of C. neoformans are the polysaccharide capsule[7], cell wall-associated melanin[8], capacity to grow at body temperature[9], and ability to produce extracellular enzymes[10] These factors together with the host state can determine the outcome of the infection. We evaluated whether Gal-3 influenced C. neoformans growth and stability of EVs. Our results demonstrate that Gal-3 plays relevant roles in C. neoformans infection primarily through direct effects on cryptococcal cells and their products
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