Stimulation of dendritic cells via the dectin-1/Syk pathway allows priming of cytotoxic T-cell responses.
The C-type lectin receptor dectin-1 functions as a pattern recognition receptor for beta-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 (DCs), rendering them competent to prime Th1 and Th17 responses. Here we show that dectin-1-activated DCs can also prime cytotoxic T-lymphocyte (CTL) responses. DCs exposed to a dectin-1 agonist induced antigen-specific expansion of TCR transgenic CD8(+) T cells and their differentiation into CTLs 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 DCs in response to IFN-gamma secreted by newly activated CD8(+) T cells. The dectin-1/Syk pathway is thus able to couple innate immune recognition of beta-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.
Leibundgut-Landmann
Salomé
S
Immunobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London, United Kingdom.
Osorio
Fabiola
F
Brown
Gordon D
GD
Reis e Sousa
Caetano
C
D000818:Animals; D017951:Antigen Presentation; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology*; D007109:Immunity; D007114:Immunization; D018664:Interleukin-12 / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D000072377:Syk Kinase; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000099181:Dectin-1
D018664:Interleukin-12; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D000099181:Dectin-1; C000606897:Syk protein, mouse