title: Card9 controls Dectin-1-induced T-cell cytotoxicity and tumor growth in mice.
abstract: Activation of the C-type lectin receptor Dectin-1 by β-glucans triggers multiple signals within DCs that result in activation of innate immunity. While these mechanisms can potently prime CD8+cytotoxic T-cell (CTL) responses without additional adjuvants, the Dectin-1 effector pathways that control CTL induction remain unclear. Here we demonstrate that Dectin-1-induced CTL cross-priming in mice does not require inflammasome activation but strictly depends on the adapter protein Card9 in vitro. In vivo, Dectin-1-mediated Card9 activation after vaccination drives both expansion and activation of Ag-specific CTLs, resulting in long-lasting CTL responses that are sufficient to protect mice from tumor challenge. This Dectin-1-induced antitumor immune response was independent of NK cell function and completely abrogated in Card9-deficient mice. Thus, our results demonstrate that Dectin-1-triggered Card9 signaling but not inflammasome activation can potently cross-prime Ag-specific CTLs, suggesting that this pathway would be a candidate for immunotherapy and vaccine development.
authors.affiliation: III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Haas
authors.affiliation: III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Heidegger
authors.affiliation: III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Wintges
authors.affiliation: III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.|Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bscheider
authors.affiliation: III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bek
authors.affiliation: III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Julius C
authors.initials: JC
authors.lastname: Fischer
authors.affiliation: III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Eisenkolb
authors.affiliation: III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Schmickl
authors.affiliation: III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Spoerl
authors.affiliation: III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Peschel
authors.affiliation: III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Poeck
authors.affiliation: Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität, Munich, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Center for Infection Research (DZIF), Munich, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Ruland
mesh_terms: D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D045142:Cross-Priming; D007113:Immunity, Innate; D058847:Inflammasomes / Q000276:immunology; D037181:Lectins, C-Type / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000503:physiopathology; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D000099181:Dectin-1
chemical_list: D053468:CARD Signaling Adaptor Proteins; D058847:Inflammasomes; D037181:Lectins, C-Type; D000099181:Dectin-1; C513280:Card9 protein, mouse
keywords: CD8+ cytotoxic T cells; Card9; Cross-priming; Dectin-1; Tumor immunity