TY - JOUR
T1 - Galectin-3 impacts Cryptococcus neoformans infection through direct antifungal effects
AU - Almeida, Fausto
AU - Wolf, Julie M.
AU - Da Silva, Thiago Aparecido
AU - Deleon-Rodriguez, Carlos M.
AU - Rezende, Caroline Patini
AU - Pessoni, André Moreira
AU - Fernandes, Fabrício Freitas
AU - Silva-Rocha, Rafael
AU - Martinez, Roberto
AU - Rodrigues, Marcio L.
AU - Roque-Barreira, Maria Cristina
AU - Casadevall, Arturo
N1 - Funding Information:
We would like to thank Johanna Rivera and Antonio Nakouzi from Albert Einsten College of Medicine, New York, USA, and Patricia Vendruscolo and Roberta Ribeiro Costa Rosales from Ribeirao Preto Medical School, Sao Paulo, Brazil, for technical support. We also thank Dr Kamila Peronni and Dr Wilson Araujo Silva Jr for RNA-seq data, and Dr Roberto Nascimento Silva for fruitful discussions and helping us to obtain RNA-seq analysis. M.L.R. acknowledges support from the Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) and from the Instituto Nacional de Ciência e Tecnologia de Inovação em Doenças de Populações Negligenciadas (INCT-IDPN). F.A. received funding from Fundação de Amparo à Pesquisa do Estado de São Paulo (2016/03322-7, 2016/15055-3)—Project Young Researcher. A.C. was supported in part by NIH awards AI033142, AI052733, and HL059842.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-017-02126-7
DO - 10.1038/s41467-017-02126-7
M3 - Article
C2 - 29213074
AN - SCOPUS:85037984563
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1968
ER -