TY - JOUR
T1 - Galectin-3 inhibits Paracoccidioides brasiliensis growth and impacts Paracoccidioidomycosis through multiple mechanisms
AU - Hatanaka, Otavio
AU - Rezende, Caroline Patini
AU - Moreno, Pedro
AU - Fernandes, Fabrício Freitas
AU - Martins Oliveira Brito, Patrícia Kellen
AU - Martinez, Roberto
AU - Coelho, Carolina
AU - Roque-Barreira, Maria Cristina
AU - Casadevall, Arturo
AU - Almeida, Fausto
N1 - Funding Information:
We thank Patricia Vendruscolo and Roberta Ribeiro Costa Rosales from Ribeirao Preto Medical School, Sao Paulo, Brazil, for technical support. F.A. received funding from Fundação de Amparo à Pesquisa do Estado de São Paulo (2016/03322-7, 2016/15055-3), Project Young Researcher, CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico, and CAPES (Coordenação de Aperfeiçoamento de Nível Superior). A.C. was supported in part by NIH awards AI033142, AI052733, and HL059842. All of the authors contributed to the research design and data analyses. O.H., C.P.R., P.M., F.F.F., P.K.M.O.B., and F.A. performed the experiments; R.M., M.C.R.-B., A.C., and F.A. contributed reagents/materials/analysis tools; O.H., C.P.R., P.M., C.C., M.C.R.-B., A.C., and F.A. wrote the paper. We declare no competing financial interests.
Publisher Copyright:
© 2019 Hatanaka et al.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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 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.
AB - 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 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.
KW - Extracellular vesicles
KW - Fungal infection
KW - Galectin-3
KW - Paracoccidioides brasiliensis
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U2 - 10.1128/MSPHERE.00209-19
DO - 10.1128/MSPHERE.00209-19
M3 - Article
C2 - 31019001
AN - SCOPUS:85065316699
SN - 2379-5042
VL - 4
JO - mSphere
JF - mSphere
IS - 2
M1 - e00209-19
ER -