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Abstract:

Fasciolosis is a trematode zoonosis of interest in public health and cattle production. We report here the immunostimulatory effect of a 66 mer mucin-like peptide from Fasciola hepatica (Fhmuc), which synergizes with lipopolysaccharide (LPS) to promote dendritic cell (DC) maturation, endowing these cells with Th1-polarizing capacity. Exposure of DCs to Fhmuc in presence of LPS induced enhanced secretion of pro-inflammatory cytokines and expression of co-stimulatory molecules by DCs, promoting their T cell stimulatory capacity and selectively augmenting IFN-3 secretion by allogeneic T cells. Furthermore, exposure of DCs to Fhmuc augmented LPS-induced Toll-like receptor (TLR) 4 expression on the cell surface. Finally, Fhmuc-conditioned DCs induced parasite specific-adaptive immunity with increased levels of IFN-3 secreted by splenocytes from vaccinated animals, and higher parasite-specific IgG antibodies. However, Fhmuc-treated DC conferred modest protection against F. hepatica infection highlighting the potent immuno-regulatory capacity of the parasite. In summary, this work highlights the capacity of a mucin-derived peptide from F. hepatica to enhance LPS-maturation of DCs and induce parasite-specific immune responses with potential implications in vaccination and therapeutic strategies. © The Author(s) 2017.

Registro:

Documento: Artículo
Título:A mucin-like peptide from Fasciola hepatica instructs dendritic cells with parasite specific Th1-polarizing activity
Autor:Noya, V.; Brossard, N.; Rodríguez, E.; Dergan-Dylon, L.S.; Carmona, C.; Rabinovich, G.A.; Freire, T.
Filiación:Laboratorio de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
Unidad de Biología Parasitaria, Instituto de Higiene, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:antibody; autacoid; cytokine; gamma interferon; glycoprotein p 15095; helminth antibody; immunoglobulin enhancer binding protein; immunoglobulin G; lipopolysaccharide; mucin 1; peptide; toll like receptor 4; animal; biological model; C57BL mouse; cell polarity; cytology; dendritic cell; drug effect; Fasciola hepatica; female; immunology; lymphocyte activation; metabolism; parasite; pathology; peritoneal cavity; signal transduction; species difference; spleen; Th1 cell; vaccination; Animals; Antibodies; Antibodies, Helminth; CD11c Antigen; Cell Polarity; Cytokines; Dendritic Cells; Fasciola hepatica; Female; Immunoglobulin G; Inflammation Mediators; Interferon-gamma; Lipopolysaccharides; Lymphocyte Activation; Mice, Inbred C57BL; Models, Biological; Mucin-1; NF-kappa B; Parasites; Peptides; Peritoneal Cavity; Signal Transduction; Species Specificity; Spleen; Th1 Cells; Toll-Like Receptor 4; Vaccination
Año:2017
Volumen:7
DOI: http://dx.doi.org/10.1038/srep40615
Título revista:Scientific Reports
Título revista abreviado:Sci. Rep.
ISSN:20452322
CAS:gamma interferon, 82115-62-6; immunoglobulin G, 97794-27-9; mucin 1, 212255-06-6; toll like receptor 4, 203811-83-0; Antibodies; Antibodies, Helminth; CD11c Antigen; Cytokines; Immunoglobulin G; Inflammation Mediators; Interferon-gamma; Lipopolysaccharides; Mucin-1; NF-kappa B; Peptides; Toll-Like Receptor 4
Registro:http://digital.bl.fcen.uba.ar/collection/paper/document/paper_20452322_v7_n_p_Noya

Referencias:

  • Merad, M., Sathe, P., Helft, J., Miller, J., Mortha, A., The dendritic cell lineage: Ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting (2013) Annu Rev Immunol, 31, pp. 563-604
  • Steinman, R.M., Decisions about dendritic cells: Past, present, and future (2012) Annu Rev Immunol, 30, pp. 1-22
  • Mogensen, T.H., Pathogen recognition and inflammatory signaling in innate immune defenses (2009) Clin Microbiol Rev, 22, pp. 240-273. , Table of Contents
  • O'Neill, L.A., Golenbock, D., Bowie, A.G., The history of Toll-like receptors-redefining innate immunity (2013) Nat Rev Immunol, 13, pp. 453-460
  • Sellge, G., Kufer, T.A., PRR-signaling pathways: Learning from microbial tactics (2015) Semin Immunol, 27, pp. 75-84
  • Kapsenberg, M.L., Dendritic-cell control of pathogen-driven T-cell polarization (2003) Nat Rev Immunol, 3, pp. 984-993
  • Hewitson, J.P., Grainger, J.R., Maizels, R.M., Helminth immunoregulation: The role of parasite secreted proteins in modulating host immunity (2009) Mol Biochem Parasitol, 167, pp. 1-11
  • Kane, C.M., Helminth antigens modulate TLR-initiated dendritic cell activation (2004) J Immunol, 173, pp. 7454-7461
  • Klaver, E.J., Trichuris suis-induced modulation of human dendritic cell function is glycan-mediated (2013) Int J Parasitol, 43, pp. 191-200
  • Zaccone, P., Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes (2003) Eur J Immunol, 33, pp. 1439-1449
  • Rondelaud, D., Vignoles, P., Abrous, M., Dreyfuss, G., The definitive and intermediate hosts of Fasciola hepatica in the natural watercress beds in central France (2001) Parasitol Res, 87, pp. 475-478
  • Dietrich, C.F., Kabaalioglu, A., Brunetti, E., Richter, (2015) J Fasciolosis. Z Gastroenterol, 53, pp. 285-290
  • Fairweather, I., Reducing the future threat from (liver) fluke: Realistic prospect or quixotic fantasy (2011) Vet Parasitol, 180, pp. 133-143
  • Piedrafita, D., Spithill, T., Smith, R., Raadsma, H., Improving animal and human health through understanding liver fluke immunology (2010) Parasite Immunol, 32, pp. 572-581
  • Toet, H., Piedrafita, D.M., Spithill, T.W., Liver fluke vaccines in ruminants: Strategies, progress and future opportunities (2014) Int J Parasitol, 44, pp. 915-927
  • Hillyer, G.V., Fasciola antigens as vaccines against fascioliasis and schistosomiasis (2005) J Helminthol, 79, pp. 241-247
  • Molina-Hernandez, V., Fasciola hepatica vaccine: We may not be there yet but we're on the right road (2015) Vet Parasitol, 208, pp. 101-111
  • Pleasance, J., Wiedosari, E., Raadsma, H.W., Meeusen, E., Piedrafita, D., Resistance to liver fluke infection in the natural sheep host is correlated with a type-1 cytokine response (2011) Parasite Immunol, 33, pp. 495-505
  • Garza-Cuartero, L., The worm turns: Trematodes steering the course of co-infections (2014) Vet Pathol, 51, pp. 385-392
  • Cardoso, F.C., Schistosoma mansoni tegument protein Sm29 is able to induce a Th1-type of immune response and protection against parasite infection (2008) PLoS Negl Trop Dis, 2, p. e308
  • Dowling, D.J., Major secretory antigens of the helminth Fasciola hepatica activate a suppressive dendritic cell phenotype that attenuates Th17 cells but fails to activate Th2 immune responses (2010) Infect Immun, 78, pp. 793-801
  • Falcon, C., Excretory-secretory products (ESP) from Fasciola hepatica induce tolerogenic properties in myeloid dendritic cells (2010) Vet Immunol Immunopathol, 137, pp. 36-46
  • Falcon, C.R., Fasciola hepatica Kunitz type molecule decreases dendritic cell activation and their ability to induce inflammatory responses (2014) PLoS One, 9, p. e114505
  • Hamilton, C.M., The Fasciola hepatica tegumental antigen suppresses dendritic cell maturation and function (2009) Infect Immun, 77, pp. 2488-2498
  • Rodriguez, E., Glycans from Fasciola hepatica Modulate the Host Immune Response and TLR-Induced Maturation of Dendritic Cells (2015) PLoS Negl Trop Dis, 9, p. e0004234
  • Falcon, C.R., Carranza, F.A., Aoki, P., Motran, C.C., Cervi, L., Adoptive transfer of dendritic cells pulsed with Fasciola hepatica antigens and lipopolysaccharides confers protection against fasciolosis in mice (2012) J Infect Dis, 205, pp. 506-514
  • Lebre, M.C., Differential expression of inflammatory chemokines by Th1-and Th2-cell promoting dendritic cells: A role for different mature dendritic cell populations in attracting appropriate effector cells to peripheral sites of inflammation (2005) Immunology and Cell Biology, 83, pp. 525-535
  • Fang, L., Heat shock protein 70 from Trichinella spiralis induces protective immunity in BALB/c mice by activating dendritic cells (2014) Vaccine, 32, pp. 4412-4419
  • Mody, N., Dubey, S., Sharma, R., Agrawal, U., Vyas, S.P., Dendritic cell-based vaccine research against cancer (2015) Expert Rev Clin Immunol, 11, pp. 213-232
  • Pizzurro, G.A., Barrio, M.M., Dendritic cell-based vaccine efficacy: Aiming for hot spots (2015) Front Immunol, 6, p. 91
  • Cancela, M., Survey of transcripts expressed by the invasive juvenile stage of the liver fluke Fasciola hepatica (2010) BMC Genomics, 11, p. 227
  • Cancela, M., Fasciola hepatica mucin-encoding gene: Expression, variability and its potential relevance in host-parasite relationship (2015) Parasitology, pp. 1-9
  • Brown, J., Wang, H., Hajishengallis, G.N., Martin, M., TLR-signaling networks: An integration of adaptor molecules, kinases, and cross-talk (2011) J Dent Res, 90, pp. 417-427
  • Ghosh, M., Subramani, J., Rahman, M.M., Shapiro, L.H., CD13 restricts TLR4 endocytic signal transduction in inflammation (2015) J Immunol, 194, pp. 4466-4476
  • Carlos, C.A., Human tumor antigen MUC1 is chemotactic for immature dendritic cells and elicits maturation but does not promote Th1 type immunity (2005) J Immunol, 175, pp. 1628-1635
  • Freire, T., Lo-Man, R., Bay, S., Leclerc, C., Tn glycosylation of the MUC6 protein modulates its immunogenicity and promotes the induction of Th17-biased T cell responses (2011) J Biol Chem, 286, pp. 7797-7811
  • Mitic, N., Milutinovic, B., Jankovic, M., CA-125 of fetal origin can act as a ligand for dendritic cell-specific ICAM-3-grabbing nonintegrin (2014) Cell Mol Biol Lett, 19, pp. 249-261
  • Stax, M.J., Mucin 6 in seminal plasma binds DC-SIGN and potently blocks dendritic cell mediated transfer of HIV-1 to CD4(+ ) T-lymphocytes (2009) Virology, 391, pp. 203-211
  • Noya, V., A mucin-like peptide from Fasciola hepatica induces parasite-specific Th1-type cell immunity (2016) Parasitol Res, 115, pp. 1053-1063
  • Vukman, K.V., Adams, P.N., O'Neill, S.M., Fasciola hepatica tegumental coat antigen suppresses MAPK signalling in dendritic cells and up-regulates the expression of SOCS3 (2013) Parasite Immunol, 35, pp. 234-238

Citas:

---------- APA ----------
Noya, V., Brossard, N., Rodríguez, E., Dergan-Dylon, L.S., Carmona, C., Rabinovich, G.A. & Freire, T. (2017) . A mucin-like peptide from Fasciola hepatica instructs dendritic cells with parasite specific Th1-polarizing activity. Scientific Reports, 7.
http://dx.doi.org/10.1038/srep40615
---------- CHICAGO ----------
Noya, V., Brossard, N., Rodríguez, E., Dergan-Dylon, L.S., Carmona, C., Rabinovich, G.A., et al. "A mucin-like peptide from Fasciola hepatica instructs dendritic cells with parasite specific Th1-polarizing activity" . Scientific Reports 7 (2017).
http://dx.doi.org/10.1038/srep40615
---------- MLA ----------
Noya, V., Brossard, N., Rodríguez, E., Dergan-Dylon, L.S., Carmona, C., Rabinovich, G.A., et al. "A mucin-like peptide from Fasciola hepatica instructs dendritic cells with parasite specific Th1-polarizing activity" . Scientific Reports, vol. 7, 2017.
http://dx.doi.org/10.1038/srep40615
---------- VANCOUVER ----------
Noya, V., Brossard, N., Rodríguez, E., Dergan-Dylon, L.S., Carmona, C., Rabinovich, G.A., et al. A mucin-like peptide from Fasciola hepatica instructs dendritic cells with parasite specific Th1-polarizing activity. Sci. Rep. 2017;7.
http://dx.doi.org/10.1038/srep40615