title: High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR.
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.
authors.affiliation: Laboratório de Imunopatologia, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: Bruna C
authors.initials: BC
authors.lastname: Favoretto
authors.affiliation: CIHIDECAR-Departmento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Adriana A C
authors.initials: AAC
authors.lastname: Casabuono
authors.affiliation: Laboratório de Imunopatologia, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: José A
authors.initials: JA
authors.lastname: Portes-Junior
authors.affiliation: LIM62-Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Jacqueline F
authors.initials: JF
authors.lastname: Jacysyn
authors.affiliation: CIHIDECAR-Departmento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Alicia S
authors.initials: AS
authors.lastname: Couto
authors.affiliation: Laboratório de Imunopatologia, Instituto Butantan, São Paulo, SP, Brazil. Electronic address: eliana.faquim@butantan.gov.br.
authors.forename: Eliana L
authors.initials: EL
authors.lastname: Faquim-Mauro
mesh_terms: D000818:Animals; D017165:Ascaris suum / Q000737:chemistry / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008351:Mannans / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D009844:Oligosaccharides / Q000276:immunology* / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology; D010767:Phosphorylcholine / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D037181:Lectins, C-Type; D008351:Mannans; D009844:Oligosaccharides; D010767:Phosphorylcholine; D010047:Ovalbumin
keywords: Ascaris suum; C-type lectin receptors; DC-Dendritic Cell; DCSIGN-Dendritic cell specifc ICAM-3 grabbing non-integrin; MR-Mannose receptor; PI - High molecular weight components from Ascaris suum extract