Galectin-3 Inhibits <named-content content-type="genus-species">Paracoccidioides brasiliensis</named-content> Growth and Impacts Paracoccidioidomycosis through Multiple Mechanisms

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 β-galactoside-binding protein, modulates important rol...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Otavio Hatanaka, Caroline Patini Rezende, Pedro Moreno, Fabrício Freitas Fernandes, Patrícia Kellen Martins Oliveira Brito, Roberto Martinez, Carolina Coelho, Maria Cristina Roque-Barreira, Arturo Casadevall, Fausto Almeida
Formato: article
Lenguaje:EN
Publicado: American Society for Microbiology 2019
Materias:
Acceso en línea:https://doaj.org/article/2885d493166443fbaff55b36cdfe10b9
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:2885d493166443fbaff55b36cdfe10b9
record_format dspace
spelling oai:doaj.org-article:2885d493166443fbaff55b36cdfe10b92021-11-15T15:22:22ZGalectin-3 Inhibits <named-content content-type="genus-species">Paracoccidioides brasiliensis</named-content> Growth and Impacts Paracoccidioidomycosis through Multiple Mechanisms10.1128/mSphere.00209-192379-5042https://doaj.org/article/2885d493166443fbaff55b36cdfe10b92019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00209-19https://doaj.org/toc/2379-5042ABSTRACT 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 β-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 β-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.Otavio HatanakaCaroline Patini RezendePedro MorenoFabrício Freitas FernandesPatrícia Kellen Martins Oliveira BritoRoberto MartinezCarolina CoelhoMaria Cristina Roque-BarreiraArturo CasadevallFausto AlmeidaAmerican Society for MicrobiologyarticleParacoccidioides brasiliensisextracellular vesiclesfungal infectiongalectin-3MicrobiologyQR1-502ENmSphere, Vol 4, Iss 2 (2019)
institution DOAJ
collection DOAJ
language EN
topic Paracoccidioides brasiliensis
extracellular vesicles
fungal infection
galectin-3
Microbiology
QR1-502
spellingShingle Paracoccidioides brasiliensis
extracellular vesicles
fungal infection
galectin-3
Microbiology
QR1-502
Otavio Hatanaka
Caroline Patini Rezende
Pedro Moreno
Fabrício Freitas Fernandes
Patrícia Kellen Martins Oliveira Brito
Roberto Martinez
Carolina Coelho
Maria Cristina Roque-Barreira
Arturo Casadevall
Fausto Almeida
Galectin-3 Inhibits <named-content content-type="genus-species">Paracoccidioides brasiliensis</named-content> Growth and Impacts Paracoccidioidomycosis through Multiple Mechanisms
description 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 β-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 β-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.
format article
author Otavio Hatanaka
Caroline Patini Rezende
Pedro Moreno
Fabrício Freitas Fernandes
Patrícia Kellen Martins Oliveira Brito
Roberto Martinez
Carolina Coelho
Maria Cristina Roque-Barreira
Arturo Casadevall
Fausto Almeida
author_facet Otavio Hatanaka
Caroline Patini Rezende
Pedro Moreno
Fabrício Freitas Fernandes
Patrícia Kellen Martins Oliveira Brito
Roberto Martinez
Carolina Coelho
Maria Cristina Roque-Barreira
Arturo Casadevall
Fausto Almeida
author_sort Otavio Hatanaka
title Galectin-3 Inhibits <named-content content-type="genus-species">Paracoccidioides brasiliensis</named-content> Growth and Impacts Paracoccidioidomycosis through Multiple Mechanisms
title_short Galectin-3 Inhibits <named-content content-type="genus-species">Paracoccidioides brasiliensis</named-content> Growth and Impacts Paracoccidioidomycosis through Multiple Mechanisms
title_full Galectin-3 Inhibits <named-content content-type="genus-species">Paracoccidioides brasiliensis</named-content> Growth and Impacts Paracoccidioidomycosis through Multiple Mechanisms
title_fullStr Galectin-3 Inhibits <named-content content-type="genus-species">Paracoccidioides brasiliensis</named-content> Growth and Impacts Paracoccidioidomycosis through Multiple Mechanisms
title_full_unstemmed Galectin-3 Inhibits <named-content content-type="genus-species">Paracoccidioides brasiliensis</named-content> Growth and Impacts Paracoccidioidomycosis through Multiple Mechanisms
title_sort galectin-3 inhibits <named-content content-type="genus-species">paracoccidioides brasiliensis</named-content> growth and impacts paracoccidioidomycosis through multiple mechanisms
publisher American Society for Microbiology
publishDate 2019
url https://doaj.org/article/2885d493166443fbaff55b36cdfe10b9
work_keys_str_mv AT otaviohatanaka galectin3inhibitsnamedcontentcontenttypegenusspeciesparacoccidioidesbrasiliensisnamedcontentgrowthandimpactsparacoccidioidomycosisthroughmultiplemechanisms
AT carolinepatinirezende galectin3inhibitsnamedcontentcontenttypegenusspeciesparacoccidioidesbrasiliensisnamedcontentgrowthandimpactsparacoccidioidomycosisthroughmultiplemechanisms
AT pedromoreno galectin3inhibitsnamedcontentcontenttypegenusspeciesparacoccidioidesbrasiliensisnamedcontentgrowthandimpactsparacoccidioidomycosisthroughmultiplemechanisms
AT fabriciofreitasfernandes galectin3inhibitsnamedcontentcontenttypegenusspeciesparacoccidioidesbrasiliensisnamedcontentgrowthandimpactsparacoccidioidomycosisthroughmultiplemechanisms
AT patriciakellenmartinsoliveirabrito galectin3inhibitsnamedcontentcontenttypegenusspeciesparacoccidioidesbrasiliensisnamedcontentgrowthandimpactsparacoccidioidomycosisthroughmultiplemechanisms
AT robertomartinez galectin3inhibitsnamedcontentcontenttypegenusspeciesparacoccidioidesbrasiliensisnamedcontentgrowthandimpactsparacoccidioidomycosisthroughmultiplemechanisms
AT carolinacoelho galectin3inhibitsnamedcontentcontenttypegenusspeciesparacoccidioidesbrasiliensisnamedcontentgrowthandimpactsparacoccidioidomycosisthroughmultiplemechanisms
AT mariacristinaroquebarreira galectin3inhibitsnamedcontentcontenttypegenusspeciesparacoccidioidesbrasiliensisnamedcontentgrowthandimpactsparacoccidioidomycosisthroughmultiplemechanisms
AT arturocasadevall galectin3inhibitsnamedcontentcontenttypegenusspeciesparacoccidioidesbrasiliensisnamedcontentgrowthandimpactsparacoccidioidomycosisthroughmultiplemechanisms
AT faustoalmeida galectin3inhibitsnamedcontentcontenttypegenusspeciesparacoccidioidesbrasiliensisnamedcontentgrowthandimpactsparacoccidioidomycosisthroughmultiplemechanisms
_version_ 1718427999799345152