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Blood, 15 December 2008, Vol. 112, No. 13, pp. 4971-4980.
Prepublished online as a Blood First Edition Paper on September 25, 2008; DOI 10.1182/blood-2008-05-158469.
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Submitted May 23, 2008
Accepted September 4, 2008
Stimulation of dendritic cells via the Dectin-1 / Syk pathway allows priming of cytotoxic T cell responses
Salome LeibundGut-Landmann, Fabiola Osorio, Gordon D Brown, and Caetano Reis e Sousa*
Immunobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London, United Kingdom
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
* Corresponding author; email: caetano{at}cancer.org.uk.
The C-type lectin receptor Dectin-1 functions as a pattern recognition receptor for  -glucans and signals via Syk kinase but independently of the Toll-like receptor (TLR) pathway to regulate expression of innate response genes. Dectin-1 signaling can promote activation of dendritic cells (DC), rendering them competent to prime Th1 and Th17 responses. Here we show that Dectin-1-activated DC can also prime cytotoxic T lymphocyte (CTL) responses. DC exposed to a Dectin-1 agonist induced antigen-specific expansion of TCR transgenic CD8+ T cells and their differentiation into CTL in vitro. Dectin-1 agonist also acted as an adjuvant for CTL crosspriming in vivo, eliciting potent CTL responses that protected mice from tumor challenge. In vitro but not in vivo, CTL crosspriming was dependent on IL-12 p70, which was produced by Dectin-1-activated DC in response to IFN- secreted by newly-activated CD8+ T cells. The Dectin-1/Syk pathway is thus able to couple innate immune recognition of -glucans to all branches of the adaptive immune system, including CD4+ T helper cells, B cells and CD8+ cytotoxic T cells. These data highlight the ability of non-TLR receptors to bridge innate and adaptive immunity and suggest that Dectin-1 agonists may constitute useful adjuvants for immunotherapy and vaccination.
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