Role of galectin-3 in the Cryptococcus neoformans infection

• Grant number: 16/03322-7
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: July 01, 2016
• End date: June 30, 2021
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Fausto Bruno dos Reis Almeida
• Grantee: Fausto Bruno dos Reis Almeida
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant(s): 21/06794-5 - Fungal extracellular vesicles: immunomodulation and cellular communication, AP.JP2
• Associated scholarship(s): 16/25167-3 - Influence of galectin-3 on course of infection by Cryptococcus neoformans, BP.MS; 16/15055-3 - Role of galectin-3 in the Cryptococcus neoformans infection, BP.JP

Abstract

Cryptococcus neoformans is the causative agent of cryptococcosis and a major pathogen for immunosuppressed individuals. C. neoformans represents a unique model in cell biology studies since it is the only eukaryotic pathogen with a polysaccharide capsule, furthermore produces vesicles containing its major virulence factor. These vesicles cross the cell wall to reach the extracellular space, where the polysaccharide is supposedly used for capsule growth or delivered into host tissues. Galectin-3, a glycan-binding protein, controls a broad spectrum of immunological functions, including cell adhesion, migration, activation, apoptosis and cytokine secretion within innate and adaptive immune compartments. During postdoctoral stage in the Albert Einstein College of Medicine of New York, we have verified that galectin-3 has lytic effect on extracellular vesicles of C. neoformans and we also have detected elevated levels of galectin-3 in the course of cryptococcosis murine experimental. These observations motivate the proposal to study the galectin-3 interference in the course of infection by C. neoformans, furthermore to better understand the effect of galectin-3 on the extracellular vesicles produced by C. neoformans. More specifically, we propose to do the following aims: (1) to dissect the responsible interactions by lytic effect of galectin-3 on the extracelular vesicles from C. neoformans, (2) to investigate the regulated expression and distribution of galectin-3 in murine tissues infected by C. neoformans, (3) to compare the survival of C. neoformans infection between wild and knockout (galectin-3 KO) mice, (4) to investigate the role of galectin-3 in the course of C. neoformans infection in mice through histopathological and immunological parameters, (5) to analyze comparatively the genic profile of the host innate immune response, during cryptococcosis by PCR Array, according to genic modulation to antifungal response, as well as in addition to compare with the genic modulation of the galectin-3 KO mice infected by C. neoformans. Our expectation is that galectin-3 may be responsible for important functions on the infection process by C. neoformans. (AU)

Scientific publications

(20)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FREITAS, MATEUS SILVEIRA; DEPERON BONATO, VANIA LUIZA; PESSONI, ANDRE MOREIRA; RODRIGUES, MARCIO L.; CASADEVALL, ARTURO; ALMEIDAA, FAUSTO. Fungal Extracellular Vesicles as Potential Targets for Immune Interventions. MSPHERE, v. 4, n. 6, NOV-DEC 2019. (16/03322-7)

BRAUER, VERONICA SOARES; REZENDE, CAROLINE PATINI; PESSONI, ANDRE MOREIRA; DE PAULA, RENATO GRACIANO; RANGAPPA, KANCHUGARAKOPPAL S.; NAYAKA, SIDDAIAH CHANDRA; GUPTA, VIJAI KUMAR; ALMEIDA, FAUSTO. Antifungal Agents in Agriculture: Friends and Foes of Public Health. BIOMOLECULES, v. 9, n. 10, OCT 2019. (16/03322-7)

REZENDE, CAROLINE PATINI; MARTINS OLIVEIRA BRITO, PATRICIA KELLEN; PESSONI, ANDRE MOREIRA; DA SILVA, THIAGO APARECIDO; GOLDMAN, GUSTAVO H.; ALMEIDA, FAUSTO. Altered expression of genes related to innate antifungal immunity in the absence of galectin-3. VIRULENCE, v. 12, n. 1, p. 981-988, JAN 1 2021. (16/03322-7, 16/25167-3)

SANTOS, PATRICK; ALMEIDA, FAUSTO. Role of Exosomal miRNAs and the Tumor Microenvironment in Drug Resistance. CELLS, v. 9, n. 6, JUN 2020. (16/03322-7)

BITENCOURT, TAMIRES APARECIDA; REZENDE, CAROLINE PATINI; QUARESEMIN, NATALIA RENAULT; MORENO, PEDRO; HATANAKA, OTAVIO; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE MARIA; ALMEIDA, FAUSTO. Extracellular Vesicles From the Dermatophyte Trichophyton interdigitale Modulate Macrophage and Keratinocyte Functions. FRONTIERS IN IMMUNOLOGY, v. 9, OCT 9 2018. (14/03847-7, 16/15055-3, 15/23435-8, 16/03322-7)

CAMPOS ANTONIETO, AMANDA CRISTINA; VIEIRA NOGUEIRA, KAROLINE MARIA; DE PAULA, RENATO GRACIANO; NORA, LUFSA CZAMANSKI; ANZOLINI CASSIANO, MURILO HENRIQUE; GUAZZARONI, MARIA-EUGENIA; ALMEIDA, FAUSTO; DA SILVA, THIAGO APARECIDO; RIES, LAURE NICOLAS ANNICK; DE ASSIS, LEANDRO JOSE; et al. A Novel Cys2His2 Zinc Finger Homolog of AZF1 Modulates Holocellulase Expression in Trichoderma reesei. MSYSTEMS, v. 4, n. 4, JUL-AUG 2019. (16/23233-9, 16/03322-7, 15/04309-1, 17/04217-5, 16/03763-3, 18/03766-8, 15/09553-8, 12/22921-8)

MARTINS OLIVEIRA-BRITO, PATRICIA KELLEN; REZENDE, CAROLINE PATINI; ALMEIDA, FAUSTO; ROQUE-BARREIRA, MARIA CRISTINA; DA SILVA, THIAGO APARECIDO. iNOS/Arginase-1 expression in the pulmonary tissue over time during Cryptococcus gattii infection. Innate Immunity, v. 26, n. 2, AUG 2019. (16/03322-7, 16/23112-7, 16/04877-2, 16/10446-4, 16/25167-3)

SANTOS, PATRICK; ALMEIDA, FAUSTO. Exosome-Based Vaccines: History, Current State, and Clinical Trials. FRONTIERS IN IMMUNOLOGY, v. 12, JUL 14 2021. (16/03322-7, 19/25826-5)

BRAUER, VERONICA S. S.; PESSONI, ANDRE M.; FREITAS, MATEUS S. S.; CAVALCANTI-NETO, MARINALDO P. P.; RIES, LAURE N. A.; ALMEIDA, FAUSTO. Chitin Biosynthesis in Aspergillus Species. JOURNAL OF FUNGI, v. 9, n. 1, p. 42-pg., 2023-01-01. (16/03322-7)

DA SILVA, THIAGO APARECIDO; ROQUE-BARREIRA, MARIA CRISTINA; CASADEVALL, ARTURO; ALMEIDA, FAUSTO. Extracellular vesicles from Paracoccidioides brasiliensis induced M1 polarization in vitro. SCIENTIFIC REPORTS, v. 6, OCT 24 2016. (16/03322-7, 13/10741-8, 13/04088-0, 16/04877-2)

HATANAKA, OTAVIO; REZENDE, CAROLINE PATINI; MORENO, PEDRO; FERNANDES, FABRICIO FREITAS; MARTINS OLIVEIRA BRITO, PATRICIA KELLEN; MARTINEZ, ROBERTO; COELHO, CAROLINA; ROQUE-BARREIRA, MARIA CRISTINA; CASADEVALL, ARTURO; ALMEIDA, FAUSTO. Galectin-3 Inhibits Paracoccidioides brasiliensis Growth and Impacts Paracoccidioidomycosis through Multiple Mechanisms. MSPHERE, v. 4, n. 2, MAR-APR 2019. (16/03322-7, 16/15055-3)

BRAUER, VERONICA S.; PESSONI, ANDRE M.; BITENCOURT, TAMIRES A.; PAULA, RENATO G. DE; ROCHA, LILIANA DE OLIVEIRA; GOLDMAN, GUSTAVO H.; ALMEIDA, FAUSTO. Extracellular Vesicles from Aspergillus flavus Induce M1 Polarization In Vitro. MSPHERE, v. 5, n. 3, MAY-JUN 2020. (16/03322-7)

ROCHA, MARINA CAMPOS; DE GODOY, KRISSIA FRANCO; BANNITZ-FERNANDES, RENATA; MARILHANO FABRI, JOAO H. T.; FERRARI BARBOSA, MAYRA M.; DE CASTRO, PATRICIA ALVES; ALMEIDA, FAUSTO; GOLDMAN, GUSTAVO HENRIQUE; DA CUNHA, ANDERSON FERREIRA; NETTO, LUIS E. S.; et al. Analyses of the three 1-Cys Peroxiredoxins from Aspergillus fumigatus reveal that cytosolic Prx1 is central to H2O2 metabolism and virulence. SCIENTIFIC REPORTS, v. 8, AUG 17 2018. (14/16636-4, 16/03322-7, 15/17541-0, 13/22375-6)

ANNICK RIES, LAURE NICOLAS; STEENWYK, JACOB L.; DE CASTRO, PATRICIA ALVES; ALMEIDA DE LIMA, POLLYNE BORBOREMA; ALMEIDA, FAUSTO; DE ASSIS, LEANDRO JOSE; MANFIOLLI, ADRIANA OLIVEIRA; TAKAHASHI-NAKAGUCHI, AZUSA; KUSUYA, YOKO; HAGIWARA, DAISUKE; et al. Nutritional Heterogeneity Among Aspergillus fumigatus Strains Has Consequences for Virulence in a Strain- and Host-Dependent Manner. FRONTIERS IN MICROBIOLOGY, v. 10, APR 24 2019. (16/03322-7, 17/14159-2)

REZENDE, CAROLINE PATINI; BRITO, PATRICIA KELLEN MARTINS OLIVEIRA; DA SILVA, THIAGO APARECIDO; PESSONI, ANDRE MOREIRA; RAMALHO, LEANDRA NAIRA ZAMBELLI; ALMEIDA, FAUSTO. Influence of Galectin-3 on the Innate Immune Response during Experimental Cryptococcosis. JOURNAL OF FUNGI, v. 7, n. 6, JUN 2021. (16/03322-7, 16/25167-3)

STEENWYK, JACOB L.; LIND, ABIGAIL L.; RIES, LAURE N. A.; DOS REIS, THAILA F.; SILVA, LILIAN P.; ALMEIDA, FAUSTO; BASTOS, RAFAEL W.; FRAGA DA SILVA, THAIS FERNANDA DE CAMPOS; BONATO, VANIA L. D.; PESSONI, ANDRE MOREIRA; et al. Pathogenic Allodiploid Hybrids of Aspergillus Fungi. Current Biology, v. 30, n. 13, p. 2495+, JUL 6 2020. (17/14159-2, 16/03322-7, 16/07870-9)

ALMEIDA, FAUSTO; WOLF, JULIE M.; DA SILVA, THIAGO APARECIDO; DELEON-RODRIGUEZ, CARLOS M.; REZENDE, CAROLINE PATINI; PESSONI, ANDRE MOREIRA; FERNANDES, FABRICIO FREITAS; SILVA-ROCHA, RAFAEL; MARTINEZ, ROBERTO; RODRIGUES, MARCIO L.; et al. Galectin-3 impacts Cryptococcus neoformans infection through direct antifungal effects. NATURE COMMUNICATIONS, v. 8, DEC 6 2017. (16/03322-7, 16/15055-3)

ALMEIDA, FAUSTO; RODRIGUES, MARCIO L.; COELHO, CAROLINA. The Still Underestimated Problem of Fungal Diseases Worldwide. FRONTIERS IN MICROBIOLOGY, v. 10, FEB 12 2019. (16/03322-7)

RIES, LAURE N. A.; PARDESHI, LAKHANSING; DONG, ZHICLIANG; TAN, KAELING; STEENWYK, JACOB L.; COLABARDINI, ANA CRISTINA; FERREIRA FILHO, JAIRE A.; DE CASTRO, PATRICIA A.; SILVA, LILIAN P.; PREITE, NYCOLAS W.; et al. The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence. PLOS PATHOGENS, v. 16, n. 7, JUL 2020. (17/14159-2, 17/21983-3, 18/25217-6, 17/07536-4, 17/01188-4, 13/50954-0, 14/00789-6, 13/07937-8, 16/07870-9, 19/09278-8, 16/03322-7)

BITENCOURT, TAMIRES A.; HATANAKA, OTAVIO; PESSONI, ANDRE M.; FREITAS, MATEUS S.; TRENTIN, GABRIEL; SANTOS, PATRICK; ROSSI, ANTONIO; MARTINEZ-ROSSI, NILCE M.; ALVES, LYSANGELA L.; CASADEVALL, ARTURO; et al. Fungal Extracellular Vesicles Are Involved in Intraspecies Intracellular Communication. MBIO, v. 13, n. 1, p. 14-pg., 2022-01-01. (19/02504-2, 19/22596-9, 16/03322-7, 19/22454-0)