title: Excretory-secretory products (ESP) from Fasciola hepatica induce tolerogenic properties in myeloid dendritic cells.
abstract: Fasciola hepatica is a helminth trematode that migrates through the host tissues until reaching bile ducts where it becomes an adult. During its migration the parasite releases different excretory-secretory products (ESP), which are in contact with the immune system. In this study, we focused on the effect of ESP on the maturation and function of murine bone marrow derived-dendritic cells (DC). We found that the treatment of DC with ESP failed to induce a classical maturation of these cells, since ESP alone did not activate DC to produce any cytokines, although they impaired the ability of DC to be activated by TLR ligands and also their capacity to stimulate an allospecific response. In addition, using an in vitro ovalbumin peptide-restricted priming assay, ESP-treated DC exhibited a capacity to drive Th2 and regulatory T cell (Treg) polarization of CD4(+) cells from DO11.10 transgenic mice. This was characterized by increased IL-4, IL-5, IL-10 and TGF-beta production and the expansion of CD4(+)CD25(+)Foxp3(+) cells. Our results support the hypothesis that ESP from F. hepatica modulate the maturation and function of DC as part of a generalized immunosuppressive mechanism that involves a bias towards a Th2 response and Treg development.
authors.affiliation: Departamento de Bioquímica Clínica, CIBICI-CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, 5000 Córdoba, Argentina.
authors.forename: Cristian
authors.initials: C
authors.lastname: Falcón
authors.forename: Franco
authors.initials: F
authors.lastname: Carranza
authors.forename: Fernando F
authors.initials: FF
authors.lastname: Martínez
authors.forename: Carolina P
authors.initials: CP
authors.lastname: Knubel
authors.forename: Diana T
authors.initials: DT
authors.lastname: Masih
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Motrán
authors.forename: Laura
authors.initials: L
authors.lastname: Cervi
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D005210:Fasciola hepatica / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D015801:Helminth Proteins / Q000502:physiology*; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015801:Helminth Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors; D016753:Interleukin-10; D015847:Interleukin-4