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Study of the involvement of DC-SIGN and MR receptors in the mechanisms of immunesuppression induced by high molecular weight components of Ascaris suum extract

Grant number: 10/10393-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2010
Effective date (End): July 31, 2014
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Eliana Faquim de Lima Mauro
Grantee:Bruna Cristina Favoretto
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Helminths, and their products are potent immunomodulators. Work carried out with extract of Ascaris suum showed that the high molecular weight components (PI) contained in it suppress the immune response induced by ovalbumin (OVA). PI inhibits the expression of MHC-II molecules and costimulatory antigen presenting cells (APCs) such as dendritic cells (DCs) and thus its ability to induce proliferation of TCD4+ cells by a mechanism dependent on IL-10. The DCs as APCs via membrane receptors recognize molecular patterns present on pathogens and direct the immune response effector. In this context, we studied the involvement of Toll-like receptors (TLR)-induced suppression in PI. We found that immunization of mice with OVA promotes increased expression of TLR1, 2 and 4 in lymphoid cells, but PI is able to inhibit the increase in cell MHC class II + cells and CD11c + purified from mice immunized with OVA + PI. Experiments conducted in mice, TLR4-/ - or TLR2-/ - PI allowed to verify that it is still able to suppress the cellular and humoral responses OVA-specific expression of molecules involved in antigen presentation of the animals immunized with OVA + PI and maturation DCs differentiated in vitro with agonists of TLRs thus excluding the participation of these receptors in immunomodulation exerted by these components Asc. Considering these results, we initiated in vitro tests with CLRs ligand (mannan) that allow us to suggest that these receptors participate in the recognition of PI and thus its immunomodulatory effect. Thus, the aim of this project is to study the involvement of C-type lectins receptors (CLRs) expressed on APCs in immunomodulation induced PI.

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. Web of Science Citations: 3.
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. Web of Science Citations: 6.
FAVORETTO, BRUNA C.; SILVA, SANDRIANA R.; JACYSYN, JACQUELINE F.; CAMARA, NIELS O. S.; FAQUIM-MAURO, ELIANA L. TLR2-and 4-independent immunomodulatory effect of high molecular weight components from Ascaris suum. Molecular Immunology, v. 58, n. 1, p. 17-26, MAR 2014. Web of Science Citations: 4.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.