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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: MSPHERE; v. 4, n. 2 MAR-APR 2019.
• Web of Science Citations: 3

Abstract

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)

• FAPESP's process: 16/03322-7 - Role of galectin-3 in the Cryptococcus neoformans infection
• Grantee: Fausto Bruno dos Reis Almeida
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 16/15055-3 - Role of galectin-3 in the Cryptococcus neoformans infection
• Grantee: Fausto Bruno dos Reis Almeida
• Support Opportunities: Scholarships in Brazil - Young Researchers