Article abstract
Nature Immunology 8, 630 - 638 (2007)
Published online: 22 April 2007 | doi:10.1038/ni1460
Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17
Salomé LeibundGut-Landmann1,
Olaf Gro
2,
Matthew J Robinson1,
Fabiola Osorio1,
Emma C Slack1,5,
S Vicky Tsoni3,
Edina Schweighoffer4,
Victor Tybulewicz4,
Gordon D Brown3,
Jürgen Ruland2
&
Caetano Reis e Sousa1
Abstract
The C-type lectin dectin-1 binds to yeast and signals through the kinase Syk and the adaptor CARD9 to induce production of interleukin 10 (IL-10) and IL-2 in dendritic cells (DCs). However, whether this pathway promotes full DC activation remains unclear. Here we show that dectin-1–Syk–CARD9 signaling induced DC maturation and the secretion of proinflammatory cytokines, including IL-6, tumor necrosis factor and IL-23, but little IL-12. Dectin-1-activated DCs 'instructed' the differentiation of CD4+ IL-17-producing effector T cells (TH-17 cells) in vitro, and a dectin-1 agonist acted as an adjuvant promoting the differentiation of TH-17 and T helper type 1 cells in vivo. Infection with Candida albicans induced CARD9-dependent TH-17 responses to the organism. Our data indicate that signaling through Syk and CARD9 can couple innate to adaptive immunity independently of Toll-like receptor signals and that CARD9 is required for the development of TH-17 responses to some pathogens.
- Immunobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London WC2A 3PX, UK.
- III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
- Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7925, South Africa.
- National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
- Present address: Department of Medicine, McMaster University Medical Center, Hamilton, Ontario L8N 3Z5, Canada.
Correspondence to: Caetano Reis e Sousa1 e-mail: caetano@cancer.org.uk
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