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Eur J Immunol. 2017 May;47(5):872-879. doi: 10.1002/eji.201646775. Epub 2017 Apr 10.

Card9 controls Dectin-1-induced T-cell cytotoxicity and tumor growth in mice.

Author information

1
III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
2
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
3
Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität, Munich, Germany.
4
German Cancer Consortium (DKTK), Heidelberg, Germany.
5
German Center for Infection Research (DZIF), Munich, Germany.

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.

KEYWORDS:

CD8+ cytotoxic T cells; Card9; Cross-priming; Dectin-1; Tumor immunity

PMID:
28295265
PMCID:
PMC5434796
DOI:
10.1002/eji.201646775
[Indexed for MEDLINE]
Free PMC Article

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