title: The Fusarium toxin deoxynivalenol disrupts phenotype and function of monocyte-derived dendritic cells in vivo and in vitro.
abstract: The trichothecene mycotoxin deoxynivalenol (DON) causes systemic immuno-suppression in pigs and possibly also in humans after chronic dietary exposure. Since the outcome of every immune response is largely controlled by dendritic cells (DC), we hypothesised that a direct influence of DON on DC function might play a role in mediating DON immunotoxicity. To test this hypothesis, a 2x2 factorial design study was performed. Pigs were fed a control diet or a diet containing DON (DON-diet); monocyte-derived DC (MoDC) from these pigs were then treated with DON in vitro or left untreated. Phenotype and function of the MoDC were analysed. In vitro DON-treatment of MoDC from pigs fed the control diet resulted in a down-regulation of CD80/86 and CD40. This was associated with an activation of the mitogen-associated protein kinases ERK1/2 and JNK. The endocytic activity of MoDC was decreased after in vitro DON-exposure while their T cell stimulatory capacity was not altered. MoDC derived from pigs that had been fed the DON-diet failed to up-regulate MHC-II in response to LPS/TNFalpha. Dietary exposure of pigs to DON inhibited endocytosis of FITC-dextran by MoDC, but did not influence T cell stimulatory capacity. ERK1/2 and JNK were constitutively activated in MoDC from pigs fed the DON-diet. If MoDC derived from pigs fed the DON-diet were exposed to DON in vitro, this resulted in an up-regulation of MHC-II and CD80/86, but not CD40. In comparison to untreated MoDC from pigs fed DON-diet, endocytic capacity was further down-regulated, whereas mitogen-activated protein kinase activation was increased. In summary, DON disrupts porcine DC function in vitro and in vivo, which might contribute to the immunosuppressive effects of this mycotoxin.
authors.affiliation: Institute of Anatomy, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany. dianebimczok@yahoo.de
authors.forename: Diane
authors.initials: D
authors.lastname: Bimczok
authors.forename: Susanne
authors.initials: S
authors.lastname: Döll
authors.forename: Henriette
authors.initials: H
authors.lastname: Rau
authors.forename: Tanja
authors.initials: T
authors.lastname: Goyarts
authors.forename: Nicole
authors.initials: N
authors.lastname: Wundrack
authors.forename: Michael
authors.initials: M
authors.lastname: Naumann
authors.forename: Sven
authors.initials: S
authors.lastname: Dänicke
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Rothkötter
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology; D005670:Fusarium / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D000922:Immunotoxins / Q000097:blood / Q000633:toxicity; D066298:In Vitro Techniques; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D009183:Mycotoxins / Q000633:toxicity*; D010641:Phenotype; D034421:Sus scrofa; D014255:Trichothecenes / Q000097:blood / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D000922:Immunotoxins; D009183:Mycotoxins; D014255:Trichothecenes; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; C007262:deoxynivalenol