Characterization of Toxoplasma gondii microneme proteins interaction with TLR2 glycans

• Grant number: 12/20809-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: February 01, 2013
• End date: July 31, 2014
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Maria Cristina Roque Antunes Barreira
• Grantee: Flávia Costa Mendonça Natividade
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Toxoplasmosis is caused by the protozoan Toxoplasma gondii, an intracellular parasite able of infecting any nucleated cell of warm-blooded animals. In the apical region of this parasite are several organelles that release a range of molecules involved in adhesion and invasion of the host cell. Some proteins released by organelles called micronemes (MICs) have adhesive domains essential for virulence of the parasite; they can associate with each other on the surface of tachyzoite, forming complexes, such as TgMIC1/MIC4/MIC6.Previously, we have demonstrated that the subcomplex TgMIC1/MIC4 binds to lactose and stimulates macrophages to secrete IL-12. More recently, experiments that have used HEK293A cells transfected with TLR2, revealed that there is recognition of N-glycans of TLR2 ectodomain by carbohydrate recognition domain of MICs, suggesting that this interaction arises in the production of IL-12 induced by TgMIC1 and TgMIC4.This idea was greatly enhanced by the observation that macrophages from TLR2-/- mice fail to respond to MICs stimulation through IL-12 production. Thus, we have strong indications that TgMIC1 and TgMIC4 interact through the lectin site with Toll-like receptors and, thus, promote the release of pro-inflammatory cytokines and modulate the immunity against the parasite.This project aims to detail the study of the microneme proteins interaction with TLR2 glycans using mutant forms of receptor for N-glycosylation sites. Therefore, we can identify glycan(s) key(s) to microneme proteins induce cell activation. In a second step, the glycan(s) key(s) will have the structure determinate for comparison with glycidic structures, target of recognition by MICs, as revealed by glycoarray

Scientific publications

(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)