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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Galectin-3 Inhibits Paracoccidioides brasiliensis Growth and Impacts Paracoccidioidomycosis through Multiple Mechanisms

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Autor(es):
Hatanaka, Otavio [1] ; Rezende, Caroline Patini [1] ; Moreno, Pedro [1] ; Fernandes, Fabricio Freitas [2] ; Martins Oliveira Brito, Patricia Kellen [2] ; Martinez, Roberto [3] ; Coelho, Carolina [4, 5] ; Roque-Barreira, Maria Cristina [2] ; Casadevall, Arturo [6] ; Almeida, Fausto [1]
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cellular & Mol Biol, Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Ribeirao Preto, SP - Brazil
[4] Univ Exeter, Coll Life & Environm Sci, Dept Biosci, Exeter, Devon - England
[5] Univ Aberdeen, Med Res Council, Ctr Med Mycol, Aberdeen - Scotland
[6] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD - USA
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: MSPHERE; v. 4, n. 2 MAR-APR 2019.
Citações Web of Science: 3
Resumo

The thermodimorphic pathogenic fungi Paracoccidioides brasiliensis and Paracoccidioides lutzii are the etiologic causes of paracoccidioidomycosis (PCM), the most prevalent systemic mycosis in Latin America. Galectin-3 (Gal-3), an animal beta-galactoside-binding protein, modulates important roles during microbial infections, such as triggering a Th2-polarized immune response in PCM. Herein, we demonstrate that Gal-3 also plays other important roles in P. brasiliensis infection. We verified that Gal-3 levels are upregulated in human and mice infections and established that Gal-3 inhibited P. brasiliensis growth by inhibiting budding. Furthermore, Gal-3 affected disruption and internalization of extracellular vesicles (EVs) from P. brasiliensis by macrophages. Our results suggest important protective roles for Gal-3 in P. brasiliensis infection, indicating that increased Gal-3 production during P. brasiliensis infection may affect fungal growth and EV stability, thus promoting beneficial effects that could influence the course of PCM. The finding that Gal-3 has effects against P. brasiliensis together with previously reported effects against Cryptococcus neoformans suggests that molecule has a general antifungal role in innate defenses against fungal pathogens. IMPORTANCE Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America. Although the immune mechanisms to control PCM are still not fully understood, several events of the host innate and adaptive immunity are crucial to determine the progress of the infection. Mammalian beta-galactoside-binding protein galectin-3 (Gal-3) plays significant roles during microbial infections and has been studied for its immunomodulatory roles, but it can also have direct antimicrobial effects. We asked whether this protein plays a role in Paracoccidioides brasiliensis. We report herein that Gal-3 indeed has direct effects on the fungal pathogen, inhibiting fungal growth and reducing extracellular vesicle stability. Our results suggest a direct role for Gal-3 in P. brasiliensis infection, with beneficial effects for the mammalian host. (AU)

Processo FAPESP: 16/03322-7 - Papel de galectina-3 na infecção por Cryptococcus neoformans
Beneficiário:Fausto Bruno dos Reis Almeida
Linha de fomento: 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
Linha de fomento: Bolsas no Brasil - Jovens Pesquisadores