Syk-dependent ERK activation regulates IL-2 and IL-10 production by DC stimulated with zymosan.
Zymosan is a particulate yeast preparation that elicits high levels of IL-2 and IL-10 from dendritic cells (DC) and engages multiple innate receptors, including the Syk-coupled receptor dectin-1 and the MyD88-coupled receptor TLR2. Here, we show that induction of IL-2 and IL-10 by zymosan requires activation of ERK MAP kinase in murine DC. Surprisingly, ERK activation in response to zymosan is completely blocked in Syk-deficient DC and unaffected by MyD88 deficiency. Conversely, ERK activation in response to the TLR2 agonist Pam3Cys is completely MyD88 dependent and unaffected by Syk deficiency. The inability of TLR2 ligands in zymosan to couple to ERK may explain the Syk dependence of the IL-2 and IL-10 response in DC and emphasises the importance of Syk-coupled pattern recognition receptors such as dectin-1 in the detection of yeasts. Furthermore, the lack of receptor compensation observed here suggests that responses induced by complex innate stimuli cannot always be predicted by the signalling pathways downstream of individual receptors.
Slack
Emma C
EC
Immunobiology Laboratory, Cancer Research UK, London Research Institute, London, UK.
Robinson
Matthew J
MJ
Hernanz-Falcón
Patricia
P
Brown
Gordon D
GD
Williams
David L
DL
Schweighoffer
Edina
E
Tybulewicz
Victor L
VL
Reis e Sousa
Caetano
C
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005936:Glucans / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D037181:Lectins, C-Type; D055666:Lipopeptides; D008074:Lipoproteins / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009570:Nitriles / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010457:Peptidoglycan / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D000072377:Syk Kinase; D015054:Zymosan / Q000494:pharmacology*; D000099181:Dectin-1
D002070:Butadienes; D003545:Cysteine; D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D005936:Glucans; D016753:Interleukin-10; D053762:Interleukin-12 Subunit p40; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D055666:Lipopeptides; D008074:Lipoproteins; D008565:Membrane Proteins; D053594:Myeloid Differentiation Factor 88; D009419:Nerve Tissue Proteins; D009570:Nitriles; D009842:Oligopeptides; D010457:Peptidoglycan; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D015054:Zymosan; D000099181:Dectin-1; C507780:Myd88 protein, mouse; C113580:U 0126; C480175:glucan phosphate; C069172:2,3-bis(palmitoyloxy)-2-propyl-1-palmitoylcysteine; C106335:macrophage stimulatory lipopeptide 2; C000606897:Syk protein, mouse; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one