Molecular mechanisms involved in the suppression of the immune response to helminths: intracellular signaling pathways induced by the interaction of Ascaris suum antigens with DC-SIGN and MR on dendritic cells

• Grant number: 14/13085-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2014
• End date: August 31, 2017
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Eliana Faquim de Lima Mauro
• Grantee: Bruna Cristina Favoretto
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Secretory/excretory products from helminths exert a suppressive effect on the immune system, ensuring its survival in the host. High molecular weight components from Ascaris suum extract (PI) directly modulate the dendritic cells (DCs) maturation, inhibiting the expression of costimulatory and MHC-II molecules and consequent lymphocytes T proliferation. This PI effect on DCs is independent of Toll-like receptors 2 and 4 (TLR2 and 4) and the MyD88 molecule. However, PI is composed by glycoconjugates containing N-linked chains that interact with C-type lectin receptors such as DC-SIGN and MR. The interaction of PI with DC-SIGN and MR results in inhibition of DCs activation when incubated with LPS. Therefore, the blockage of DC-SIGN and MR prevents the PI-binding on DCs and allows the cell maturation in the presence of LPS. This inhibitory effect observed with Asc antigens (PI) has been described with other helminthes and is part of the immune escape mechanism of these parasites. However, the molecular mechanisms involved in this immunosuppression are poorly understood. In this sense, in this project we aim to study the signaling pathways triggered by the recognition of PI by DC-SIGN and MR in DCs and its interference on the cell activation by a TLR4 ligand. We intend with this study to contribute to new insights into the modulation of TLR pathway activation, as TLR4, on DCs by the CLRs through the recognition of helminth antigens. (AU)

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)

FREITAS, A. P.; FAVORETTO, B. C.; CLISSA, P. B.; SAMPAIO, S. C.; FAQUIM-MAURO, E. L.. Crotoxin Isolated from Crotalus durissus terrificus Venom Modulates the Functional Activity of Dendritic Cells via Formyl Peptide Receptors. JOURNAL OF IMMUNOLOGY RESEARCH, 2018. (14/13085-7, 10/10393-1, 15/15608-0, 11/23735-0)

FREITAS, A. P.; FAVORETTO, B. C.; CLISSA, P. B.; SAMPAIO, S. C.; FAQUIM-MAURO, E. L.. Crotoxin Isolated from Crotalus durissus terrificus Venom Modulates the Functional Activity of Dendritic Cells via Formyl Peptide Receptors. JOURNAL OF IMMUNOLOGY RESEARCH, v. 2018, p. 15-pg., 2018-01-01. (14/13085-7, 10/10393-1, 15/15608-0, 11/23735-0)

FAVORETTO, BRUNA C.; CASABUONO, ADRIANA A. C.; PORTES-JUNIOR, JOSE A.; JACYSYN, JACQUELINE F.; COUTO, ALICIA S.; FAQUIM-MAURO, ELIANA L.. High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Molecular Immunology, v. 87, p. 33-46, JUL 2017. (11/23735-0, 10/01134-2, 10/10393-1, 14/13085-7, 15/15608-0)