PMID- 31019001 OWN - NLM STAT- MEDLINE DCOM- 20190520 LR - 20230121 IS - 2379-5042 (Electronic) IS - 2379-5042 (Linking) VI - 4 IP - 2 DP - 2019 Apr 24 TI - Galectin-3 Inhibits Paracoccidioides brasiliensis Growth and Impacts Paracoccidioidomycosis through Multiple Mechanisms. LID - 10.1128/mSphere.00209-19 [doi] LID - e00209-19 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 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. CI - Copyright (c) 2019 Hatanaka et al. FAU - Hatanaka, Otavio AU - Hatanaka O AD - Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil. FAU - Rezende, Caroline Patini AU - Rezende CP AD - Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil. FAU - Moreno, Pedro AU - Moreno P AD - Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil. FAU - Freitas Fernandes, Fabricio AU - Freitas Fernandes F AD - Department of Cellular and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil. FAU - Oliveira Brito, Patricia Kellen Martins AU - Oliveira Brito PKM AD - Department of Cellular and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil. FAU - Martinez, Roberto AU - Martinez R AD - Department of Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil. FAU - Coelho, Carolina AU - Coelho C AD - Department of Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom. AD - Medical Research Council Centre for Medical Mycology, University of Aberdeen, Aberdeen, United Kingdom. FAU - Roque-Barreira, Maria Cristina AU - Roque-Barreira MC AD - Department of Cellular and Molecular Biology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil. FAU - Casadevall, Arturo AU - Casadevall A AUID- ORCID: 0000-0002-9402-9167 AD - Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. FAU - Almeida, Fausto AU - Almeida F AUID- ORCID: 0000-0002-3782-3698 AD - Department of Biochemistry and Immunology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil fbralmeida@usp.br. LA - eng GR - MR/N006364/1/MRC_/Medical Research Council/United Kingdom GR - R01 HL059842/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190424 PL - United States TA - mSphere JT - mSphere JID - 101674533 RN - 0 (Antifungal Agents) RN - 0 (Blood Proteins) RN - 0 (Galectin 3) RN - 0 (Galectins) RN - 0 (LGALS3 protein, human) RN - 0 (Lgals3 protein, mouse) SB - IM MH - Animals MH - Antifungal Agents MH - Blood Proteins MH - Disease Models, Animal MH - Extracellular Vesicles MH - Galectin 3/*genetics/immunology MH - Galectins MH - Humans MH - Immunity, Innate MH - Macrophages/microbiology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Microbial Viability MH - Paracoccidioides/*growth & development MH - Paracoccidioidomycosis/*immunology MH - Up-Regulation PMC - PMC6483048 OTO - NOTNLM OT - Paracoccidioides brasiliensis OT - extracellular vesicles OT - fungal infection OT - galectin-3 EDAT- 2019/04/26 06:00 MHDA- 2019/05/21 06:00 PMCR- 2019/04/24 CRDT- 2019/04/26 06:00 PHST- 2019/04/26 06:00 [entrez] PHST- 2019/04/26 06:00 [pubmed] PHST- 2019/05/21 06:00 [medline] PHST- 2019/04/24 00:00 [pmc-release] AID - 4/2/e00209-19 [pii] AID - mSphere00209-19 [pii] AID - 10.1128/mSphere.00209-19 [doi] PST - epublish SO - mSphere. 2019 Apr 24;4(2):e00209-19. doi: 10.1128/mSphere.00209-19.