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Lectin from pathogens

Grant number: 13/04088-0
Support type:Research Projects - Thematic Grants
Duration: November 01, 2013 - October 31, 2017
Field of knowledge:Biological Sciences - Immunology - Immunochemistry
Principal researcher: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
Pesquisadores principais:
Maria Célia Jamur
Assoc. researchers:Ademilson Panunto-Castelo
Associated grant(s):16/11984-0 - Paracoccin induces M1 polarization of macrophages via interaction with TLR4, PUB.ART
16/50004-0 - Dissecting the paracoccin interaction with toll-like receptors N-glycans: a necessary step in the design of a novel immunomodulatory agent applicable to confer protection against fungal diseases, AP.R SPRINT
16/04651-4 - IL-17 Induction by ArtinM is Due to Stimulation of IL-23 and IL-1 Release and/or Interaction with CD3 in CD4+ T Cells, PUB.ART
16/06379-0 - Neutrophils contribute to the protection conferred by ArtinM against intracellular pathogens: A study on Leishmania major, PUB.ART
Associated scholarship(s):17/06251-6 - Impact of paracoccin overexpression in the biology and virulence of Paracoccidioides spp. conidia, BP.PD
17/17289-4 - Interaction of Toxoplasma gondii lectins with natural killer Toll like receptors, BP.IC
16/00629-4 - Characterization of enzymatic and lectin domains and the effects on innate immunity cell receptors , BP.PD
+ associated scholarships 14/22561-7 - Overexpression of paracoccin: phenotype and virulence of Paracoccidioides brasiliensis strains, BP.DR
15/14111-4 - Characterization of TgMIC1 and TgMIC4 immunomodulatory potential: analysis of the pleiotropic effect and repercussions on immunity, BP.PD
14/13259-5 - Do immunomodulatory lectins of Toxoplasma gondii confer protection against Leishmania major infection?, BP.IC
14/16003-1 - Effect of adoptive transfer of spleen cells or CD4+ T cells stimulated with ArtinM during infection with Paracoccidioides brasiliensis, BP.IC
14/13260-3 - Does Paracoccidioides brasiliensis-derived lectin confers protection against Leishmania major infection?, BP.IC
14/05359-0 - Distribution of paracoccin on the surface of Paracoccidioides brasiliensis and interaction with innate immunity cell receptors: role in the acute phase of paracoccidioidomycosis, BP.PD
14/05362-0 - Characterization of TgMIC1 and TgMIC4 immunomodulatory potential: analysis of pleiotropic effect and repercussions on adaptive immunity, BP.PD - associated scholarships

Abstract

Our group has regularly investigated the recognition of glycans on host cells by pathogen lectins; we have also studied the biological responses triggered by such recognition. Our team has focused on particular lectins: (i) TgMIC1 and TgMIC4 - proteins secreted by micronemes of the protozoan Toxoplasma gondii that recognize glycans bearing sialic acid and beta-galactose as terminal residues, respectively; (ii) paracoccin, proteins of the surface of Paracoccidioides brasiliensis yeasts that recognize N-acetylglucosamine. In these cases, we have isolated the proteins by affinity chromatography on columns of their specific sugar; we have also characterized the structure and biological properties of the native forms of each of these lectins. The relevance of the activities performed by these proteins have motivated us to clone the gene codifying each lectin and express it heterologously. We have characterized the resulting recombinant proteins in terms of their ability to reproduce the properties of the corresponding native lectin. Functional studies revealed that the lectins derived from T. gondii and P. Brasiliensis play relevant roles in pathogen biology and affect host cell immunity. We have examined the recognition involved in the induction of these effects, the identification of molecules containing the recognition target, the cell signaling triggered by this recognition, the cellular responses stemming from cell activation, and the consequent production of immunological modulators as well as the resistance conferred by these processes. Concerning the Toxoplasma gondii lectins, we currently aim to (i) characterize their interaction with the N-glycans associated with TLR4, in the same way that we have proceeded in the case of TLR2; (ii) establish the structure of TLRs N-glycans identified as recognition targets of T. gondii and implicated in cell activation; (iii) conduct molecular modeling of TLR2 glycans and their interaction with TgMIC1; (iv) express TgMIC1 and TgMIC4 in Pichia pastoris, instead of Escherichia coli, to obtain a soluble LPS-free recombinant protein. As for the lectin paracoccin, we aim to (i) determine its expression in mycelia and mycellium-yeast transition forms of P. brasiliensis, and compare it with its expression in yeasts; (ii) characterize the interaction of paracoccin with innate immunity cell receptors, especially TLR2, targeting the requirement for receptor heterodimerization and the participation of accessory proteins; (iii) find out whether the interaction between paracoccin and TRL2 depends on carbohydrate recognition and, if this is the case, (iv) identify whether the ectodomain N-glycan(s) is(are) the target(s) of this recognition, (v) investigate paracoccin-modulation of the expression of these receptors in innate immunity cells and of the citokies production by these same cells; (vi) determine the effect of paracoccin administration to mice with respect to the pattern of citokines production and PRRs expression in phagocytes; (vii) characterize the effect of N-glycans on the activities of glucanase and amylase of P. brasiliensis yeasts as well as systematically analyze the role of AMPc on N-acetylglucosaminidase expression; (viii) determine the part played by N-glycans in the activity of P. brasiliensis enzymes and identify non-N-glycosilated proteins by DIGE - Difference gel electrophoresis), .These aims will be sought by our local group in collaboration with other research groups abroad, more specifically the teams led by Professor Nicholas Gay (University of Cambridge, UK), Prof. Igor de Almeida (University of Texas in El Paso, USA), Prof. Stephen Mathews (Imperial College, London, UK), and Prof. Ten Feizi (Imperial College, London, UK). (AU)

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Scientific publications (19)
(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)
MILANEZ, GUILHERME P.; WERLE, CATIERINE H.; AMORIM, MARIENE R.; RIBEIRO, RAFAEL A.; TIBO, LUIZ H. S.; ROQUE-BARREIRA, MARIA CRISTINA; OLIVEIRA, ALINE F.; BROCCHI, MARCELO. HU-Lacking Mutants of Salmonella enterica Enteritidis Are Highly Attenuated and Can Induce Protection in Murine Model of Infection. FRONTIERS IN MICROBIOLOGY, v. 9, . (13/04088-0, 12/05382-6, 14/13412-8, 14/05359-0)
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, . (16/10446-4, 06/60642-2, 14/16003-1, 16/04877-2, 16/23112-7, 13/04088-0, 12/09611-0)
FERNANDES, FABRICIO F.; OLIVEIRA, ALINE F.; LANDGRAF, TAISE N.; CUNHA, CRISTINA; CARVALHO, AGOSTINHO; VENDRUSCOLO, PATRICIA E.; GONCALES, RELBER A.; ALMEIDA, FAUSTO; DA SILVA, THIAGO A.; RODRIGUES, FERNANDO; et al. Impact of Paracoccin Gene Silencing on Paracoccidioides brasiliensis Virulence. MBIO, v. 8, n. 4, . (14/05359-0, 14/22561-7, 16/04877-2, 13/04088-0, 12/09611-0, 16/00629-4)
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, . (16/10446-4, 14/16003-1, 16/04877-2, 16/23112-7, 13/04088-0, 12/09611-0)
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, . (13/10741-8, 13/04088-0, 16/03322-7, 16/04877-2)
DA SILVA, THIAGO APARECIDO; MARIANO, VANIA SAMMARTINO; SARDINHA-SILVA, ALINE; DE SOUZA, MARIA APARECIDA; PATRIARCA MINEO, TIAGO WILSON; ROQUE-BARREIRA, MARIA CRISTINA. IL-17 Induction by ArtinM is Due to Stimulation of IL-23 and IL-1 Release and/or Interaction with CD3 in CD4(+) T Cells. PLoS One, v. 11, n. 2, . (06/60642-2, 12/12950-0, 10/51763-6, 13/04088-0, 12/09611-0)
CECILIO, NERRY TATIANA; CARVALHO, FERNANDA CAROLINE; LIU, YAN; MONCRIEFFE, MARTIN; DE ALMEIDA BURANELLO, PATRICIA ANDRESSA; ZORZETTO-FERNANDES, ANDRE LUIZ; DALLE LUCHE, DOUGLAS; HANNA, EBERT SEIXAS; SOARES, SANDRO GOMES; FEIZI, TEN; et al. Yeast expressed ArtinM shares structure, carbohydrate recognition, and biological effects with native ArtinM. International Journal of Biological Macromolecules, v. 82, p. 22-30, . (09/16146-9, 13/04088-0)
MENDONCA-NATIVIDADE, FLAVIA COSTA; LOPES, CARLA DUQUE; RICCI-AZEVEDO, RAFAEL; SARDINHA-SILVA, ALINE; PINZAN, CAMILA FIGUEIREDO; PAIVA ALEGRE-MALLER, ANA CLAUDIA; NOHARA, LILIAN L.; CARNEIRO, ALAN B.; PANUNTO-CASTELO, ADEMILSON; ALMEIDA, IGOR C.; et al. Receptor Heterodimerization and Co-Receptor Engagement in TLR2 Activation Induced by MIC1 and MIC4 from Toxoplasma gondii. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 20, n. 20, . (13/04088-0, 17/02998-0, 14/13324-1)
SARDINHA-SILVA, ALINE; MENDONCA-NATIVIDADE, FLAVIA C.; PINZAN, CAMILA F.; LOPES, CARLA D.; COSTA, DIEGO L.; JACOT, DAMIEN; FERNANDES, FABRICIO F.; ZORZETTO-FERNANDES, ANDRE L. V.; GAY, NICHOLAS J.; SHER, ALAN; et al. The lectin-specific activity of Toxoplasma gondii microneme proteins 1 and 4 binds Toll-like receptor 2 and 4 N-glycans to regulate innate immune priming. PLOS PATHOGENS, v. 15, n. 6, . (12/12950-0, 14/13324-1, 13/04088-0)
ASSIS-MARQUES, MARIANA APRIGIO; OLIVEIRA, ALINE FERREIRA; RUAS, LUCIANA PEREIRA; DOS REIS, THAILA FERNANDA; ROQUE-BARREIRA, MARIA CRISTINA; RODRIGUES COELHO, PAULO SERGIO. Saccharomyces cerevisiae Expressing Gp43 Protects Mice against Paracoccidioides brasiliensis Infection. PLoS One, v. 10, n. 3, . (13/04088-0, 06/60642-2, 14/05359-0)
POLLI, CLAUDIA DANELLA; RUAS, LUCIANA PEREIRA; VERONEZ, LUCIANA CHAIN; GERALDINO, THAIS HERRERO; DE MORAIS, FABIANA ROSSETTO; ROQUE-BARREIRA, MARIA CRISTINA; PEREIRA-DA-SILVA, GABRIELA. Jacalin-Activated Macrophages Exhibit an Antitumor Phenotype. BIOMED RESEARCH INTERNATIONAL, . (13/04088-0)
RICCI-AZEVEDO, RAFAEL; OLIVEIRA, ALINE FERREIRA; CONRADO, MARINA C. A. V.; CARVALHO, FERNANDA CAROLINE; ROQUE-BARREIRA, MARIA CRISTINA. Neutrophils Contribute to the Protection Conferred by ArtinM against Intracellular Pathogens: A Study on Leishmania major. PLoS Neglected Tropical Diseases, v. 10, n. 4, . (13/04088-0, 12/13419-7)
LIU, Y.; CECILIO, N. T.; CARVALHO, F. C.; ROQUE-BARREIRA, M. C.; FEIZI, T.. Glycan microarray analysis of the carbohydrate-recognition specificity of native and recombinant forms of the lectin ArtinM. DATA IN BRIEF, v. 5, p. 1035-1047, . (09/16146-9, 13/04088-0)
GONCALES, RELBER AGUIAR; RICCI-AZEVEDO, RAFAEL; VIEIRA, VANESSA C. S.; FERNANDES, FABRICIO F.; THOMAZ, SANDRA M. DE O.; CARVALHO, AGOSTINHO; VENDRUSCOLO, PATRICIA E.; CUNHA, CRISTINA; ROQUE-BARREIRA, MARIA CRISTINA; RODRIGUES, FERNANDO. Paracoccin Overexpression in Paracoccidioides brasiliensis Enhances Fungal Virulence by Remodeling Chitin Properties of the Cell Wall. Journal of Infectious Diseases, v. 224, n. 1, p. 164-174, . (14/22561-7, 17/02998-0, 13/04088-0, 18/21708-5, 16/00629-4)
RICCI-AZEVEDO, RAFAEL; COSTA MENDONCA-NATIVIDADE, FLAVIA; CAROLINA SANTANA, ANA; ALCOFORADO DINIZ, JULIANA; CRISTINA ROQUE-BARREIRA, MARIA. Microneme Proteins 1 and 4 From Toxoplasma gondii Induce IL-10 Production by Macrophages Through TLR4 Endocytosis. FRONTIERS IN IMMUNOLOGY, v. 12, . (16/10446-4, 18/21708-5, 17/02998-0, 14/13324-1, 13/04088-0, 16/14657-0)
BURANELLO, PATRICIA A. A.; BARBOSA-LORENZI, VALERIA C.; PINTO, MARCELO R.; PEREIRA-DA-SILVA, GABRIELA; BARREIRA, MARIA CRISTINA R. A.; JAMUR, MARIA CELIA; OLIVER, CONSTANCE. The lectin ArtinM activates RBL-2H3 mast cells without inducing degranulation. PLoS One, v. 15, n. 3, . (09/54013-0, 13/04088-0, 06/60642-2, 17/18618-1)
DA SILVA, THIAGO APARECIDO; FERNANDES, FABRICIO FREITAS; ROQUE-BARREIRA, MARIA CRISTINA. Data on IL-17 production induced by plant lectins. DATA IN BRIEF, v. 7, p. 1584-1587, . (13/04088-0, 06/60642-2, 12/09611-0)
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, . (16/10446-4, 10/02122-8, 12/12950-0, 09/16146-9, 16/04877-2, 13/04088-0, 12/09611-0)
SANTOS, ADRIANO; CARVALHO, FERNANDA C.; ROQUE-BARREIRA, MARIA-CRISTINA; ZORZETTO-FERNANDES, ANDRE LUIZ; GIMENEZ-ROMERO, DAVID; MONZO, ISIDRO; BUENO, PAULO R.. Evidence for Conformational Mechanism on the Binding of TgMIC4 with beta-Galactose-Containing Carbohydrate Ligand. Langmuir, v. 31, n. 44, p. 12111-12119, . (13/04088-0, 09/11520-0)

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