title: A mucin-like peptide from Fasciola hepatica instructs dendritic cells with parasite specific Th1-polarizing activity.
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-γ 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-γ 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.
authors.affiliation: Laboratorio de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de La República, Montevideo, Uruguay.
authors.forename: Verónica
authors.initials: V
authors.lastname: Noya
authors.affiliation: Laboratorio de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de La República, Montevideo, Uruguay.
authors.forename: Natalie
authors.initials: N
authors.lastname: Brossard
authors.affiliation: Laboratorio de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de La República, Montevideo, Uruguay.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Rodríguez
authors.affiliation: Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
authors.forename: L Sebastián
authors.initials: LS
authors.lastname: Dergan-Dylon
authors.affiliation: Unidad de Biología Parasitaria, Instituto de Higiene, Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
authors.forename: Carlos
authors.initials: C
authors.lastname: Carmona
authors.affiliation: Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.|Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Rabinovich
authors.affiliation: Laboratorio de Inmunomodulación y Desarrollo de Vacunas, Departamento de Inmunobiología, Facultad de Medicina, Universidad de La República, Montevideo, Uruguay.
authors.forename: Teresa
authors.initials: T
authors.lastname: Freire
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D000909:Antibodies, Helminth / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D005210:Fasciola hepatica / Q000276:immunology / Q000378:metabolism*; D005260:Female; D007074:Immunoglobulin G / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D018396:Mucin-1 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010271:Parasites / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D010529:Peritoneal Cavity; D015398:Signal Transduction / Q000187:drug effects; D013045:Species Specificity; D013154:Spleen / Q000473:pathology; D018417:Th1 Cells / Q000166:cytology* / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014611:Vaccination
chemical_list: D000906:Antibodies; D000909:Antibodies, Helminth; D039521:CD11c Antigen; D016207:Cytokines; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D018396:Mucin-1; D016328:NF-kappa B; D010455:Peptides; D051197:Toll-Like Receptor 4; D007371:Interferon-gamma