Effect of lectin ArtinM on murine CD4+ T and CD8+ T cells

• Grant number: 12/09611-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): September 01, 2012
• Effective date (End): April 30, 2016
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Maria Cristina Roque Antunes Barreira
• Grantee: Thiago Aparecido da Silva
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The lectin ArtinM, extracted from seeds of Artocarpus heterophyllus and characterized as a homotetramer consisted of is endowed with interesting biological properties: (1) it activates neutrophils through the recognition of N-glycans attached to CXCR2 and TLR2 receptors; (2) induces degranulation of mast cells by interacting with N-glycans of FcµR or to N-glycans of IgE bound to FcµR; (3) stimulates the production of IL-12 through the recognition of N-glycans of the TLR2 ectodomain, expressed on the surface of antigen presenting cells (APCs); (4) exerts immunomodulatory activity, which accounts for Th1 immunity (5) confers resistance to intracellular pathogens, such as P. brasiliensis, Leishmania amazonensis and Leishmania major, Neospora caninum e Candida albicans.CD4+ T cells participate in essential functions of the immune system can lead subpopulations cells suitable for generating efficient response to against pathogens, maintenance of tolerance and regulation of immunity. The effector function of CD8+ T cells (cytotoxic T lymphocyte, or CTL), in turn, is essential to control a variety of parasitic infections of intracellular pathogen. The cytotoxicity occurs by a mechanism involving the production of perforinas and granzymes, and the expression of FasL/CD95L membrane.This study is to analyze the effects of lectin ArtinM in CD4+ and CD8+ T cells murine, as for their differentiation and activation, as well as changes in their survival. There also, will be investigated the mechanisms responsible for the observed effects, which includes identifying glycotarget recognized by ArtinM and involved in signaling that triggers cellular response to stimulation with the lectin. This proposal is based on preliminary results indicate that ArtinM leads directly to activation of CD4+ T cell and induce to cytokine production by Th1 and Th17 profiles; these effects were display to be dependent on the recognition of glycans present in subunit ³ receptor CD3, involving signaling molecules PI3K PTK, p42/44MAPK, p38MAPK, JNK e PKC.The preliminary study will be investigated by evaluating the expression of costimulatory and inhibitory molecules, induction of cell differentiation and cell aggregation, cytokine production and cytotoxic activity; will also be expanded in order to assess the activation of CD8+ T cells. In addition, will investigate the survival of CD4+ and CD8+ T cells after stimulation with ArtinM, as well as identified signaling molecules related to this process. Finally, the glycans investigate constituents of the surface of CD4+ and CD8+ T cells involved in the specificity of ArtinM.Keywords: Lectins, ArtinM, CD4+ T cells and CD8+ T cells.

Scientific publications

(9)

(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)

PAIVA ALEGRE-MALLER, ANA CLAUDIA; MENDONCA, FLAVIA COSTA; DA SILVA, THIAGO APARECIDO; OLIVEIRA, ALINE FERREIRA; FREITAS, MATEUS SILVEIRA; HANNA, EBERT SEIXAS; ALMEIDA, IGOR C.; GAY, NICHOLAS J.; ROQUE-BARREIRA, MARIA CRISTINA. Therapeutic Administration of Recombinant Paracoccin Confers Protection against Paracoccidioides brasiliensis Infection: Involvement of TLRs. PLoS Neglected Tropical Diseases, v. 8, n. 12, DEC 2014. (13/14161-6, 12/20809-6, 14/05359-0, 12/09611-0, 10/01112-9)

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. (14/16003-1, 16/23112-7, 16/10446-4, 16/04877-2, 12/09611-0, 13/04088-0)

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, FEB 22 2016. (10/51763-6, 12/09611-0, 06/60642-2, 13/04088-0, 12/12950-0)

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, JUL 2017. (14/16003-1, 16/23112-7, 16/10446-4, 16/04877-2, 06/60642-2, 12/09611-0, 13/04088-0)

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, JUL-AUG 2017. (16/00629-4, 14/05359-0, 14/22561-7, 16/04877-2, 12/09611-0, 13/04088-0)

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, JUN 2016. (12/09611-0, 13/04088-0, 06/60642-2)

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. (16/10446-4, 16/04877-2, 13/04088-0, 12/09611-0, 10/02122-8, 09/16146-9, 12/12950-0)

DA SILVA, THIAGO APARECIDO; DE SOUZA, MARIA APARECIDA; CECILIO, NERRY TATIANA; ROQUE-BARREIRA, MARIA CRISTINA. Activation of spleen cells by ArtinM may account for its immunomodulatory properties. Cell and Tissue Research, v. 357, n. 3, p. 719-730, SEP 2014. (12/09611-0, 10/51763-6, 06/60642-2)

FREITAS, MATEUS S.; OLIVEIRA, ALINE F.; DA SILVA, THIAGO A.; FERNANDES, FABRICIO F.; GONCALES, RELBER A.; ALMEIDA, FAUSTO; ROQUE-BARREIRA, MARIA C.. Paracoccin Induces M1 Polarization of Macrophages via Interaction with TLR4. FRONTIERS IN MICROBIOLOGY, v. 7, JUL 5 2016. (13/10741-8, 12/09611-0)