title: TLR2- and 4-independent immunomodulatory effect of high molecular weight components from Ascaris suum.
abstract: Components of high molecular-weight (PI) obtained from Ascaris suum extract down-regulate the Th1/Th2-related immune responses induced by ovalbumin (OVA)-immunization in mice. Furthermore, the PI down-modulates the ability of dendritic cells (DCs) to activate T lymphocytes by an IL-10-mediated mechanism. Here, we evaluated the role of toll like receptors 2 and 4 (TLR2 and 4) in the modulatory effect of PI on OVA-specific immune response and the PI interference on DC full activation. An inhibition of OVA-specific cellular and humoral responses were observed in wild type (WT) or in deficient in TLR2 (TLR2(-/-)) or 4 (TLR4(-/-)) mice immunized with OVA plus PI when compared with OVA-immunized mice. Low expression of class II MHC, CD40, CD80 and CD86 molecules was observed in lymph node (LN) cells from WT, TLR2(-/-) or TLR4(-/-) mice immunized with OVA plus PI compared with OVA-primed cells. We also verified that PI was able to modulate the activation of DCs derived from bone marrow of WT, TLR2(-/-) or TLR4(-/-) mice induced in vitro by agonists of TLRs, as observed by a decreased expression of class II MHC and costimulatory molecules and by low secretion of pro-inflammatory cytokines. Its effect was accompanied by IL-10 synthesis. In this sense, the modulatory effect of PI on specific-immune response and DC activation is independent of TLR2 or TLR4.
authors.affiliation: Laboratory of Immunopathology, Butantan Institute, São Paulo, SP, Brazil.
authors.forename: Bruna C
authors.initials: BC
authors.lastname: Favoretto
authors.affiliation: Pasteur Institute, São Paulo, Brazil.
authors.forename: Sandriana R
authors.initials: SR
authors.lastname: Silva
authors.affiliation: LIM62 Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Jacqueline F
authors.initials: JF
authors.lastname: Jacysyn
authors.affiliation: Department of Immunology, University of São Paulo, São Paulo, Brazil.
authors.forename: Niels O S
authors.initials: NO
authors.lastname: Câmara
authors.affiliation: Laboratory of Immunopathology, Butantan Institute, São Paulo, SP, Brazil. Electronic address: elianafaquim@butantan.gov.br.
authors.forename: Eliana L
authors.initials: EL
authors.lastname: Faquim-Mauro
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D001196:Ascariasis / Q000276:immunology*; D017165:Ascaris suum / Q000276:immunology*; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D019013:CD40 Antigens / Q000096:biosynthesis; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D056747:Immunomodulation; D016753:Interleukin-10 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
chemical_list: D000947:Antigens, Helminth; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; C556062:IL10 protein, mouse; D008565:Membrane Proteins; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D010047:Ovalbumin
keywords: APC; Asc; Ascaris suum; Ascaris suum extract; C-type lectin receptor; CLR; DC; DTH; Dendritic Cells; Dendritic cell; ELISA; High molecular weight components; High molecular weight components from Ascaris suum; Immunoregulation; PI; TLR2; TLR4; Toll like receptor 2 (TLR2); Toll like receptor 4 (TLR4); antigen presenting cell; delayed-type hypersensitivity reaction; enzyme linked immunosorbent assay; toll like receptor 2; toll like receptor 4