Galectin-3 impacts Cryptococcus neoformans infection through direct antifungal effects

Autor(es):Mostrar menos -

Almeida, Fausto ^[1] ; Wolf, Julie M. ^[2] ; da Silva, Thiago Aparecido ^[3] ; DeLeon-Rodriguez, Carlos M. ^[2] ; Rezende, Caroline Patini ^[1] ; Pessoni, Andre Moreira ^[1] ; Fernandes, Fabricio Freitas ^[3] ; Silva-Rocha, Rafael ^[3] ; Martinez, Roberto ^[4] ; Rodrigues, Marcio L. ^{[5, 6]} ; Roque-Barreira, Maria Cristina ^[3] ; Casadevall, Arturo ^[7]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Yeshiva Univ, Dept Microbiol & Immunol, Albert Einstein Coll Med, New York, NY 10461 - USA

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cellular & Mol Biol, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Dept Internal Med, Ribeirao Preto Med Sch, BR-14048900 Ribeirao Preto, SP - Brazil

^[5] Univ Fed Rio de Janeiro, Inst Microbiol Paulo de Goes, BR-21941902 Rio De Janeiro - Brazil

^[6] Fundacao Oswaldo Cruz Fiocruz, CDTS, BR-21041361 Rio De Janeiro - Brazil

^[7] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 - USA

• Tipo de documento: Artigo Científico
• Fonte: NATURE COMMUNICATIONS; v. 8, DEC 6 2017.
• Citações Web of Science: 19

Resumo

Cryptococcus neoformans is an encapsulated fungal pathogen that causes cryptococcosis, which is a major opportunistic infection in immunosuppressed individuals. Mammalian beta-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. (AU)

• Processo FAPESP: 16/03322-7 - Papel de galectina-3 na infecção por Cryptococcus neoformans
• Beneficiário: Fausto Bruno dos Reis Almeida
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 16/15055-3 - Papel de galectina-3 na infecção por Cryptococcus neoformans
• Beneficiário: Fausto Bruno dos Reis Almeida
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores