Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor


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. © 2017 Elsevier Ltd


Documento: Artículo
Título:High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR
Autor:Favoretto, B.C.; Casabuono, A.A.C.; Portes-Junior, J.A.; Jacysyn, J.F.; Couto, A.S.; Faquim-Mauro, E.L.
Filiación:Laboratório de Imunopatologia, Instituto Butantan, São Paulo, SP, Brazil
CIHIDECAR-Departmento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
LIM62–Universidade de São Paulo, São Paulo, Brazil
Palabras clave: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; asparagine linked oligosaccharide; CD209 antigen; Freund adjuvant; granulocyte macrophage colony stimulating factor; high molecular weight component; interleukin 4; mannan; mannose receptor; natural products and their synthetic derivatives; ovalbumin; unclassified drug; lectin; oligosaccharide; phosphorylcholine; animal cell; animal experiment; Article; Ascaris suum; binding affinity; binding assay; bound fraction; Canavalia ensiformis; cell activation; cell surface; cell suspension; confocal microscopy; dendritic cell; flow cytometry; immunization; in vitro study; internalization; lectin binding; lymphocyte proliferation; male; matrix assisted laser desorption ionization time of flight mass spectrometry; molecular weight; mouse; nonhuman; priority journal; protein content; purification; retention time; T lymphocyte; animal; Ascaris suum; Bagg albino mouse; cell proliferation; chemistry; dendritic cell; drug effects; immunology; lymphocyte activation; Animals; Ascaris suum; Cell Proliferation; Dendritic Cells; Lectins, C-Type; Lymphocyte Activation; Male; Mannans; Mice; Mice, Inbred BALB C; Molecular Weight; Oligosaccharides; Ovalbumin; Phosphorylcholine; T-Lymphocytes
Página de inicio:33
Página de fin:46
Título revista:Molecular Immunology
Título revista abreviado:Mol. Immunol.
CAS:Freund adjuvant, 9007-81-2; mannan, 51395-96-1, 9036-88-8; ovalbumin, 77466-29-6; phosphorylcholine, 107-73-3; Lectins, C-Type; Mannans; Oligosaccharides; Ovalbumin; Phosphorylcholine


  • Alves, M.J., Abuin, G., Kuwajima, V.Y., Colli, W., Partial inhibition of trypomastigote entry into cultured mammalian cells by monoclonal antibodies against a surface glycoprotein of Trypanosoma cruzi (1986) Mol. Biochem. Parasitol., 21, pp. 75-82
  • Baldo, C., Jamora, C., Yamanouye, N., Zorn, T.M., Moura-da-Silva, A.M., Mechanisms of vascular damage by hemorrhagic snake venom metalloproteinases: tissue distribution and in situ hydrolysis (2010) PLoS Negl. Trop. Dis., 6, p. e727
  • Brattig, N.W., Bazzocchi, C., Kirschning, C.J., Reiling, N., Büttner, D.W., Ceciliani, F., The major surface protein of Wolbachia endosymbionts in filarial nematodes elicits immune responses through TLR2 and TLR4 (2004) J. Immunol., 173, pp. 437-445
  • Burgdorf, S., Kautz, A., Böhnert, V., Knolle, P.A., Kurts, C., Distinct pathways of antigen uptake and intracellular routing in CD4 and CD8 T cell activation (2007) Science, 5824, pp. 612-616
  • Chieppa, M., Bianchi, G., Doni, A., Del Prete, A., Sironi, M., Laskarin, G., Monti, P., Allavena, P., Cross-linking of the mannose receptor on monocyte-derived dendritic cells activates an anti-inflammatory immunosuppressive program (2003) J. Immunol., 171, pp. 4552-4560
  • Den Dunnen, J., Gringhuis, S.I., Geijtenbeek, T.B., Innate signaling by the C-type lectin DC-SIGN dictates immune responses (2009) Cancer Immunol. Immunother., 58, pp. 1149-1157
  • Du, L., Liu, L., Yu, Y., Shan, H., Li, L., Trichinella spiralis excretory-secretory products protect against polymicrobial sepsis by suppressing MyD88 via mannose receptor (2014) BioMed Res. Int., 2014, p. 898646
  • Duschak, V.G., Couto, A.S., Cruzipain, the major cysteine protease of Trypanosoma cruzi: A sulfated glycoprotein antigen as relevant candidate for vaccine development and drug target (2009) Curr. Med. Chem., 16, pp. 3174-3202
  • Engering, A., Van Vliet, S.J., Geijtenbeek, T.B., Van Kooyk, Y., Subset of DC-SIGN(+) dendritic cells in human blood transmits HIV-1 to T lymphocytes (2002) Blood, 100, pp. 1780-1786
  • Erdmann, H., Steeg, C., Koch-Nolte, F., Fleischer, B., Jacobs, T., Sialylated ligands on pathogenic Trypanosoma cruzi interact with Siglec-E (sialic acid-binding Ig-like lectin-E) (2009) Cell. Microbiol., 11, pp. 1600-1611
  • Everts, B., Hussaarts, L., Driessen, N.N., Meevissen, M.H., Schistosome-derived omega-1 drives Th2 polarization by suppressing protein synthesis following internalization by the mannose receptor (2012) J. Exp. Med., 209 (10), pp. 1753-1767. , (S1)
  • Faquim-Mauro, E.L., Macedo, M.S., The immunosuppressive activity of Ascaris suum is due to high molecular weight components (1998) Clin. Exp. Immunol., 114, pp. 245-251
  • Favoretto, B.C., Silva, S.R., Jacysyn, J.F., Câmara, N.O., Faquim-Mauro, E.L., TLR2- and 4-independent immunomodulatory effect of high molecular weight components from Ascaris suum (2014) Mol. Immunol., 58, pp. 17-26
  • Favoretto, B.C., Evaluation of Participation of Receptors Toll like Receptors and C Type Lectins Receptors in Suppressing The Immune Response Induced by High Molecular Weight Components of Ascaris suum Extract. 78 f. Thesis (MA) (2010), Institute of Biomedical Sciences, University of São Paulo São Paulo; Ferreira, A.P., Faquim, E.S., Abrahamsohn, I.A., Macedo, M.S., Immunization with Ascaris suum extract impairs T cell functions in mice (1995) Cell. Immunol., 162, pp. 202-210
  • Finkelman, F.D., Pearce, E.J., Urban, J.F., Jr., Sher, A., Regulation and biological function of helminth-induced cytokine responses (1991) Immunol. Today, 12, pp. 62-66
  • Gause, W.C., Ekkens, M., Nguyen, D., Mitro, V., Liu, Q., Finkelman, F.D., Greenwald, R.J., Urban, J.F., The development of CD4+ T effector cells during the type 2 immune response (1999) Immunol. Res., 20, pp. 55-65
  • Geijtenbeek, T.B.H., Gringhuis, S.I., Signalling through C-type lectin receptors: shaping immune responses (2009) Nat. Rev. Immunol., 9, pp. 465-479
  • Geijtenbeek, T.B., Kwon, D.S., Torensma, R., van Vliet, S.J., van Duijnhoven, G.C., Middel, J., DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells (2000) Cell, 100, pp. 587-597
  • Geijtenbeek, T.B., Van Vliet, S.J., Koppel, E.A., Sanchez-Hernandez, M., Vandenbroucke-Grauls, C.M., Appelmelk, B., Van Kooyk, Y., Mycobacteria target DC-SIGN to suppress dendritic cell function (2003) J. Exp. Medicine, 197, pp. 7-17
  • Geijtenbeek, T.B., van Vliet, S.J., Engering, A., Hart, B.A., van Kooyk, Y., Self- and nonself-recognition by C-type lectins on dendritic cells (2004) Annu. Rev. Immunol., 22, pp. 33-54
  • Gringhuis, S.I., C-type lectin DC-SIGN modulates Toll-like receptor signaling via Raf-1 kinase-dependent acetylation of transcription factor NF-kappaB (2007) Immunity, 5, pp. 605-616
  • Haig, D.M., Lima, G.C., Mota, I., Antibody suppression in mice infected with Nippostrongylus brasiliensis (1980) Parasite Immunol. Autumn., 2 (3), pp. 175-187
  • Halary, F., Amara, A., Lortat-Jacob, H., Messerle, M., Delaunay, T., Houlès, C., Human cytomegalovirus binding to DC-SIGN is required for dendritic cell infection and target cell trans-infection (2002) Immunity, 17, pp. 653-664
  • Hamilton, C.M., Dowling, D.J., Loscher, C.E., Morphew, R.M., Brophy, P.M., O'Neill, S.M., The Fasciola hepatica tegumental antigen suppresses dendritic cell maturation and function (2009) Infect. Immun., 6, pp. 2488-2498
  • Harnett, W., Rzepecka, J., Houston, K.M., How do nematodes transfer phosphorylcholine to carbohydrates? (2010) Trends Parasitol., 26, pp. 114-118
  • Hubo, M., Trinschek, B., Kryczanowsky, F., Tuettenberg, A., Steinbrink, K., Jonuleit, H., Costimulatory molecules on immunogenic versus tolerogenic human dendritic cells (2013) Front. Immunol., 82, pp. 1-14
  • Jang-Lee, J., Curwen, R.S., Ashton, P.D., Tissot, B., Mathieson, W., Panico, M., Glycomics analysis of Schistosoma mansoni egg and cercarial secretions (2007) Mol. Cell Proteomics, 6, pp. 1485-1499
  • Klaver, E.J., Kuijk, L.M., Laan, L.C., Kringel, H., van Vliet, S.J., Bouma, G., Trichuris suis-induced modulation of human dendritic cell function is glycan-mediated (2013) Int. J. Parasitol., 43, pp. 191-200
  • Maizels, R.M., Yazdanbakhsh, M., Immune regulation by helminth parasites: cellular and molecular mechanisms (2003) Nat. Rev. Immunol., 9, pp. 733-744
  • McGuirk, P., McCann, C., Mills, K.H., Pathogen-specific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates interleukin 10 production by dendritic cells: a novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis (2002) J. Exp. Med., 2, pp. 221-231
  • Moll, H., Dendritic cells and host resistance to infection (2003) Cell. Microbiol., 5, pp. 493-500
  • Morelle, W., Haslam, S.M., Olivier, V., Appleton, J.A., Morris, H.R., Dell, A., Phosphorylcholine-containing N-glycans of Trichinella spiralis: identification of multiantennary lacdiNAc structures (2000) Glycobiology, 9, pp. 941-950
  • Mosmann, T.R., Sad, S., The expanding universe of T-cell subsets: Th1, Th2 and more (1996) Immunol. Today, 17, pp. 138-146
  • Nyame, A.K., Debose-Boyd, R., Long, T.D., Tsang, V.C., Cummings, R.D., Expression of Lex antigen in Schistosoma japonicum and S.haematobium and immune responses to Lex in infected animals: lack of Lex expression in other trematodes and nematodes (1998) Glycobiology, 8, pp. 615-624
  • Pöltl, G., Kerner, D., Paschinger, K., Wilson, I.B., N-glycans of the porcine nematode parasite Ascaris suum are modified with phosphorylcholine and core fucose residues (2007) FEBS J., 274, pp. 714-726
  • Piras, M.M., Henríquez, D., Piras, R., The effect of fetuin and other sialoglycoproteins on the in vitro penetration of Trypanosoma cruzi trypomastigotes into fibroblastic cells (1987) Mol. Biochem. Parasitol., 22, pp. 135-143
  • Sallusto, F., Cella, M., Danieli, C., Lanzavecchia, A., Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products (1995) J. Exp. Med., 182, pp. 389-400
  • Schnare, M., Barton, G.M., Holt, A.C., Takeda, K., Akira, S., Medzhitov, R., Toll-like receptors control activation of adaptive immune responses (2001) Nat. Immunol., 2, pp. 947-950
  • Silva, S.R., Jacysyn, J.F., Macedo, M.S., Faquim-Mauro, E.L., Immunosuppressive components of Ascaris suum down-regulate expression of costimulatory molecules and function of antigen-presenting cells via an IL-10-mediated mechanism (2006) J. Immunol., 36, pp. 3227-3237
  • Soares, M.F.M., Mota, I., Macedo, M.S., Isolation of Ascaris suum components which suppress IgE antibody responses (1992) Int. Archs. Allergy Immunol., 97, pp. 37-43
  • Son, Y.I., Egawa, S., Tatsumi, T., Redlinger, R.E., Jr., Kalinski, P., Kanto, T., A novel bulk-culture method for generating mature dendritic cells from mouse bone marrow cells (2002) J. Immunol. Methods, 262, pp. 145-157
  • Sorvillo, N., Pos, W., van den Berg, L.M., Fijnheer, R., Martinez-Pomares, L., Geijtenbeek, T.B., The macrophage mannose receptor promotes uptake of ADAMTS13 by dendritic cells (2012) J. Blood, 119, pp. 3828-3835
  • Svajger, U., Anderluh, M., Jeras, M., Obermajer, N., C-type lectin DC-SIGN: an adhesion, signalling and antigen-uptake molecule that guides dendritic cells in immunity (2010) Cell. Signal., 10, pp. 1397-1405
  • Takeda, K., Kaisho, T., Akira, S., Toll-like receptors (2003) Annu. Rev. Immunol., 21, pp. 335-376
  • Terrazas, C.A., Sánchez-Muñoz, F., Mejía-Domínguez, A.M., Amezcua-Guerra, L.M., Terrazas, L.I., Cestode antigens induce a tolerogenic-like phenotype and inhibit LPS inflammatory responses in human dendritic cells (2011) Int. J. Biol. Sci., 9, pp. 1391-1400
  • Terrazas, C.A., Alcántara-Hernández, M., Bonifaz, L., Terrazas, L.I., Satoskar, A.R., Helminth-excreted/secreted products are recognized by multiple receptors on DCs to block the TLR response and bias Th2 polarization in a cRAF dependent pathway (2013) FASEB J., 27, pp. 4547-4560
  • Van Die, I., Cummings, R.D., Glycans modulate immune responses in helminth infections and allergy (2006) Chem. Immunol. Allergy, 90, pp. 91-112
  • Van Die, I., Van Stijn, C.M., Geyer, H., Geyer, R., Structural and functional analysis of glycosphingolipids of Schistosoma mansoni (2010) Methods Enzymol., 480, pp. 117-140
  • Van Kooyk, Y., Geijtenbeek, T.B., DC-SIGN: escape mechanism for pathogens (2003) Nat. Rev. Immunol., 3, pp. 697-709
  • Van Liempt, E., van Vliet, S.J., Engering, A., García Vallejo, J.J., Bank, C.M., Sanchez-Hernandez, M., Schistossoma mansoni soluble egg antigens are internalized by human dendritic cells through multiple C-type lectins and suppress TLR-induced dendritic cell activation (2007) Mol. Immunol., 44, pp. 2605-2615
  • Van der Kleij, D., Van Remoortere, A., Schuitemaker, J.H., Kapsenberg, M.L., Deelder, A.M., Tielens, A.G., Triggering of innate immune responses by schistosome egg glycolipids and their carbohydrate epitope GalNAc beta 1-4(Fuc alpha 1-2Fuc alpha 1-3)GlcNAc (2002) J. Infect. Dis., 185, pp. 531-539
  • Varki, A., Essentials of Glycobiology (2009), 2nd ed. Cold Spring Harbor Laboratory Press New York; Varki, A., Sialic acids as ligands in recognition phenomena (1997) FASEB J., 4, pp. 248-255


---------- APA ----------
Favoretto, B.C., Casabuono, A.A.C., Portes-Junior, J.A., Jacysyn, J.F., Couto, A.S. & Faquim-Mauro, E.L. (2017) . High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Molecular Immunology, 87, 33-46.
---------- CHICAGO ----------
Favoretto, B.C., Casabuono, A.A.C., Portes-Junior, J.A., Jacysyn, J.F., Couto, A.S., Faquim-Mauro, E.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 87 (2017) : 33-46.
---------- MLA ----------
Favoretto, B.C., Casabuono, A.A.C., Portes-Junior, J.A., Jacysyn, J.F., Couto, A.S., Faquim-Mauro, E.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, vol. 87, 2017, pp. 33-46.
---------- VANCOUVER ----------
Favoretto, B.C., Casabuono, A.A.C., Portes-Junior, J.A., Jacysyn, J.F., Couto, A.S., Faquim-Mauro, E.L. High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Mol. Immunol. 2017;87:33-46.