title: Danger signaling through the inflammasome acts as a master switch between tolerance and sensitization.
abstract: Efficient priming of adaptive immunity depends on danger signals provided by innate immune pathways. As an example, inflammasome-mediated activation of caspase-1 and IL-1beta is crucial for the development of reactive T cells targeting sensitizers like dinitrofluorobenzene (DNFB). Surprisingly, DNFB and dinitrothiocyanobenzene provide cross-reactive Ags yet drive opposing, sensitizing vs tolerizing, T cell responses. In this study, we show that, in mice, inflammasome-signaling levels can be modulated to turn dinitrothiocyanobenzene into a sensitizer and DNFB into a tolerizer, and that it correlates with the IL-6 and IL-12 secretion levels, affecting Th1, Th17, and regulatory T cell development. Hence, our data provide the first evidence that the inflammasome can define the type of adaptive immune response elicited by an Ag, and hint at new strategies to modulate T cell responses in vivo.
authors.affiliation: Departments of Dermatology and Pathology/Immunology, Geneva University Hospitals and University of Geneva, Michel-Servet 1, Geneva, Switzerland.
authors.forename: Hideki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Samuel
authors.initials: S
authors.lastname: Gehrke
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Contassot
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Roques
authors.forename: Jürg
authors.initials: J
authors.lastname: Tschopp
authors.forename: Peter S
authors.initials: PS
authors.lastname: Friedmann
authors.forename: Lars E
authors.initials: LE
authors.lastname: French
authors.forename: Olivier
authors.initials: O
authors.lastname: Gaide
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D020170:Caspase 1 / Q000276:immunology; D003429:Cross Reactions / Q000187:drug effects / Q000276:immunology; D004136:Dinitrobenzenes / Q000494:pharmacology*; D004139:Dinitrofluorobenzene / Q000494:pharmacology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000941:Antigens; D004136:Dinitrobenzenes; C508600:IL6 protein, human; D053583:Interleukin-1beta; D007376:Interleukin-2; D015850:Interleukin-6; D004139:Dinitrofluorobenzene; D020170:Caspase 1; C010936:2,4-dinitrothiocyanatobenzene