title: The Toll-like receptor-2/6 agonist macrophage-activating lipopeptide-2 cooperates with IFN-gamma to reverse the Th2 skew in an in vitro allergy model.
abstract: Dendritic cells (DC) are the most potent APCs with the capacity to induce, modulate, or shut down immune function. These features make them potentially useful for treating diseases associated with misled immunologic responses. Therefore, it was the aim of this study to reverse the allergen-dependent Th2 reaction responsible for allergic symptoms by modulating DC function. This issue was addressed in an in vitro test system consisting of human monocyte-derived allergen-pulsed DC from allergics cocultured with autologous lymphocytes. A Th2 reaction judged by the amplification of IL-4 and the down-regulation of IFN-gamma was induced by pulsing DC with the relevant allergen. To modulate this reaction, the Toll-like receptor 2/6 engaging mycoplasmal lipopetide macrophage-activating lipopeptide 2 kDa was combined with IFN-gamma to stimulate allergen-pulsed DC. Such treatment resulted in a 500-fold increase in IFN-gamma production in the supernatant of cocultured autologous lymphocytes, while the Th2 marker IL-4 was not affected. This phenomenon was associated with an increase in proliferation and the number of IFN-gamma-producing lymphocytes. Phenotype and function of thus treated DC remained stable. These data indicate that a former allergen-dependent Th2 reaction can be reversed toward a Th1-type response by an appropriate treatment of DC.
authors.affiliation: Fraunhofer Institute of Toxicology and Experimental Medicine, Department of Immunology, Allergology, and Clinical Inhalation, Hannover, Germany. weigt@item.fraunhofer.de
authors.forename: Henning
authors.initials: H
authors.lastname: Weigt
authors.forename: Peter F
authors.initials: PF
authors.lastname: Muhlradt
authors.forename: Michael
authors.initials: M
authors.lastname: Larbig
authors.forename: Norbert
authors.initials: N
authors.lastname: Krug
authors.forename: Armin
authors.initials: A
authors.lastname: Braun
mesh_terms: D039741:Antigens, Dermatophagoides / Q000276:immunology; D060829:Arthropod Proteins; D001426:Bacterial Proteins / Q000502:physiology*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003546:Cysteine Endopeptidases; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004338:Drug Combinations; D004357:Drug Synergism; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis; D055666:Lipopeptides; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008262:Macrophage Activation; D008562:Membrane Glycoproteins / Q000819:agonists*; D009842:Oligopeptides / Q000502:physiology*; D021122:Protein Subunits / Q000096:biosynthesis / Q000502:physiology; D011956:Receptors, Cell Surface / Q000819:agonists*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D001426:Bacterial Proteins; D004338:Drug Combinations; D055666:Lipopeptides; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D021122:Protein Subunits; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495368:TLR6 protein, human; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; C106335:macrophage stimulatory lipopeptide 2; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1