Galectin-3 inhibits Paracoccidioides brasiliensis growth and impacts paracoccidioidomycosis through multiple mechanisms

Hatanaka, O.; Rezende, C. P.; Moreno, P.; Fernandes, F. F.; Oliveira-Brito, P. K. M.; Martinez, R.; Coelho, C.; Roque-Barreira, M. C.; Casadevall, A.; Almeida, F.

doi:10.1101/557918

bioRxiv · 10.1101/557918

Galectin-3 inhibits Paracoccidioides brasiliensis growth and impacts paracoccidioidomycosis through multiple mechanisms

Hatanaka, O.·Rezende, C. P.·Moreno, P.·Fernandes, F. F.·Oliveira-Brito, P. K. M.·Martinez, R.·Coelho, C.·Roque-Barreira, M. C.·Casadevall, A.·Almeida, F.

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Abstract

The thermodimorphic pathogenic fungi Paracoccidioides brasiliensis and Paracoccioidioides 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 Gal-3 levels are upregulated in human and mice infections and establish that Gal-3 inhibits P. brasiliensis growth by inhibiting budding. Furthermore, Gal-3 affects disruption and internalization of extracellular vesicles (EV) from P. brasiliensis by macrophages. Our results suggest important roles for Gal-3 in P. brasiliensis infection, indicating that increased Gal-3 production during P. brasiliensis infection may account for affecting the fungal growth and EV stability, promoting a benefic course of experimental PCM. IMPORTANCEParacoccidiodomycosis (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 P. brasiliensis. We report herein that Gal-3 indeed has direct effects on fungal pathogen, inhibiting fungal growth and reducing extracellular vesicles stability. Our results suggest a direct role for Gal-3 in P. brasiliensis infection, with beneficial effects for the mammalian host.

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Hatanaka, O., Rezende, C. P., Moreno, P., Fernandes, F. F., Oliveira-Brito, P. K. M., Martinez, R., Coelho, C., Roque-Barreira, M. C., Casadevall, A., Almeida, F.. 2019-02-23. Galectin-3 inhibits Paracoccidioides brasiliensis growth and impacts paracoccidioidomycosis through multiple mechanisms. https://doi.org/10.1101/557918

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