High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR

Author(s)

Favoretto, Bruna C. ; Casabuono, Adriana A. C. ; Portes-Junior, Jose A. ; Jacysyn, Jacqueline F. ; Couto, Alicia S. ; Faquim-Mauro, Eliana L.

• Document type: Journal article
• Source: Molecular Immunology; v. 87, p. 33-46, JUL 2017.
• Web of Science Citations: 6

Abstract

Helminths, as well as their secretory/excretory products, induce a tolerogenic immune microenvironment. High molecular weight components (PI) from Ascaris suum extract down-modulate the immune response against ovalbumin (OVA). The PI exerts direct effect on dendritic cells (DCs) independent of TLR 2, 4 and MyD88 molecule and, thus, decreases the T lymphocytes response. Here, we studied the glycoconjugates in PI and the role of C-type lectin receptors (CLRs), DC-SIGN and MR, in the modulation of DCs activity. Our data showed the presence of glycoconjugates with high mannose- and complex-type N-linked oligosaccharide chains and phosphorylcholine residues on PI. In addition, these N-linked glycoconjugates inhibited the DCs maturation induced by LPS. The binding and internalization of PI-Alexa were decreased on DCs previously incubated with mannan, anti-DC-SIGN and/or anti-MR antibodies. In agreement with this, the incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished the down-modulatory effect of PI on these cells. It was also observed that the blockage of CLRs, DC-SIGN and MR on DCs reverted the inhibitory effect of PI in in vitro T cells proliferation. Therefore, our data show the involvement of DC-SIGN and MR in the recognition and consequent modulatory effect of N-glycosylated components of PI on DCs. (C) 2017 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 11/23735-0 - Mechanisms involved in the modulation of the immune response induced by high molecular weight components of Ascaris suum extract and crotoxin isolated from Crotalus durissus terrificus venom
• Grantee: Eliana Faquim de Lima Mauro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/01134-2 - Processing of metalloproteinase from Bothrops venom: activation of the catalytic activity by removal of pro-domain
• Grantee: José Antonio Portes Junior
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/10393-1 - 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
• Grantee: Bruna Cristina Favoretto
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/13085-7 - 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
• Grantee: Bruna Cristina Favoretto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/15608-0 - Evaluation of the molecular mechanisms involved in the modulation of immune response by high molecular weight components of Ascaris suum, crotoxin and phospholipase A2 from Crotalus durissus terrificus venom
• Grantee: Eliana Faquim de Lima Mauro
• Support Opportunities: Regular Research Grants