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...
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American Society for Microbiology
2019
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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) |
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Paracoccidioides brasiliensis extracellular vesicles fungal infection galectin-3 Microbiology QR1-502 |
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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 |
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