title: Fasciola hepatica tegumental coat antigen suppresses MAPK signalling in dendritic cells and up-regulates the expression of SOCS3.
abstract: Fasciola hepatica tegumental coat antigen (FhTeg) suppresses dendritic cell maturation and function by inhibiting IL-6, tumour necrosis factor (TNF)-α, IL-10 and IL-12 production and CD80, CD86 and CD40 cell surface marker expression in TLR4-stimulated dendritic cells. Fasciola hepatica also impairs dendritic cell function by inhibiting its phagocytic capacity and its ability to prime T cells. We have shown previously that activation of mast cells with bacterial ligands is also inhibited by FhTeg. Fasciola hepatica suppresses LPS-induced NF-κB and MAPK pathway (ERK) activation in these cells. Previously, we demonstrated that FhTeg induces expression of suppressor of cytokine signalling (SOCS)3, a negative regulator of the TLR pathway in mast cells. In this study, we show the same inhibitory effect of FhTeg on the activation of the other members of the MAPKs pathway (ERK, p38, JNK) in dendritic cells and demonstrate an enhanced expression of SOCS3, but not SOCS1, SOCS5 or PIAS3 in this process. These studies enhance our understanding of the immunomodulatory effect of helminth molecules on the TLR pathway.
authors.affiliation: Parasite Immune Modulation Group, School of Biotechnology, Faculty of Science and Health, Dublin City University, Dublin, Ireland.
authors.forename: K V
authors.initials: KV
authors.lastname: Vukman
authors.forename: P N
authors.initials: PN
authors.lastname: Adams
authors.forename: S M
authors.initials: SM
authors.lastname: O'Neill
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology; D005210:Fasciola hepatica / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D000947:Antigens, Helminth; D008070:Lipopolysaccharides; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D020928:Mitogen-Activated Protein Kinases
keywords: Fasciola hepatica; cell signalling; dendritic cell; immune modulation