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Mechanisms of immunomodulation by ArtinM: basis for the development of new anti-fungal therapy

Grant number: 16/10446-4
Support type:Regular Research Grants
Duration: February 01, 2017 - January 31, 2019
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Maria Cristina Roque Antunes Barreira
Grantee:Maria Cristina Roque Antunes Barreira
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Our group has evaluated the immunomodulation against pathogens by carbohydrate recognition on cell surface. We reported the ability of different lectins to modulate the immune system, as follows: mammal (Galectin-3), parasite (TgMIC1 and TgMIC4 from Toxoplasma gondii), fungus (Paracoccin from Paracoccidioides brasiliensis), and plant (ArtinM from Artocarpus heterophyllus). ArtinM showed important immunomodulatory activity that is associated with Th1 immune response, which is triggered by ArtinM binding with TLR2-N-glycans. The ArtinM immunomodulatory activity utilizes the IL-12 production by macrophages and dendritic cells. Moreover, ArtinM interacts with CXCR2 on neutrophils, FcµR on mast cells, and CD3 on lymphocytes; the ArtinM binding with different cells favors a protective immune response against intracellular pathogens. Considering the ArtinM effects is essential to study the mechanisms involved in the immunomodulation triggered by ArtinM on immune cells. Therefore, we propose to expand the analysis of mechanisms related to ArtinM effects on innate immune cells; and also to expand the investigation of the ArtinM effects on adaptive immune cells. Previous studies demonstrate that ArtinM acts on CD4+ T cells inducing a Th17 immune response, and also a Th1 profile, which contribute in therapy against fungal infection. However, several studies demonstrated that approach of antifungal drugs is limited and the modulation of immune response is important to eliminate systemic mycoses. Then, we propose to expand the application of ArtinM immunomodulatory activity on fungal infections, as follows: investigate the ArtinM effects associated with conventional antifungal drugs against experimental paracoccidioidomycosis; to develop strategies of cellular therapy on treatment of fungal infection through cellular activation triggered by ArtinM. Our proposal allows the development, in collaboration with chemical, of synthetic structures that mimic the immunomodulatory activity induced by carbohydrate recognition. (AU)

Scientific publications (6)
(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)
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. Web of Science Citations: 0.
MARTINS OLIVEIRA-BRITO, PATRICIA KELLEN; ROQUE-BARREIRA, MARIA CRISTINA; DA SILVA, THIAGO APARECIDO. The Response of IL-17-Producing B Cells to ArtinM Is Independent of Its Interaction with TLR2 and CD14. Molecules, v. 23, n. 9 SEP 2018. Web of Science Citations: 0.
RICCI-AZEVEDO, RAFAEL; ROQUE-BARREIRA, MARIA-CRISTINA; GAY, NICHOLAS J. Targeting and Recognition of Toll-Like Receptors by Plant and Pathogen Lectins. FRONTIERS IN IMMUNOLOGY, v. 8, DEC 18 2017. Web of Science Citations: 9.
MARTINS OLIVEIRA BRITO, PATRICIA KELLEN; GONCALVES, THIAGO ELEUTERIO; FERNANDES, FABRICIO FREITAS; MIGUEL, CAMILA BOTELHO; RODRIGUES, WELLINGTON FRANCISCO; LAZO CHICA, JAVIER EMILIO; ROQUE-BARREIRA, MARIA CRISTINA; DA SILVA, THIAGO APARECIDO. Systemic effects in naive mice injected with immunomodulatory lectin ArtinM. PLoS One, v. 12, n. 10 OCT 30 2017. Web of Science Citations: 4.
DA SILVA, THIAGO APARECIDO; ZORZETTO-FERNANDES, ANDRE L. V.; CECILIO, NERRY T.; SARDINHA-SILVA, ALINE; FERNANDES, FABRICIO FREITAS; ROQUE-BARREIRA, MARIA CRISTINA. CD14 is critical for TLR2-mediated M1 macrophage activation triggered by N-glycan recognition. SCIENTIFIC REPORTS, v. 7, AUG 1 2017. Web of Science Citations: 12.
DA SILVA, THIAGO APARECIDO; MARTINS OLIVEIRA-BRITO, PATRICIA KELLEN; GONCALVES, THIAGO ELEUTERIO; VENDRUSCOLO, PATRICIA EDIVANIA; ROQUE-BARREIRA, MARIA CRISTINA. ArtinM Mediates Murine T Cell Activation and Induces Cell Death in Jurkat Human Leukemic T Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 18, n. 7 JUL 2017. Web of Science Citations: 5.

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