Syk-dependent ERK activation regulates IL-2 and IL-10 production by DC stimulated with zymosan

@article{citeulike:1363726, abstract = {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.}, address = {Immunobiology Laboratory, Cancer Research UK, London Research Institute, London, UK; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, USA; National Institute for Medical Research, London, UK; Department of Medicine, McMaster University, Hamilton, Ontario, Canada}, author = {Emma c and Matthew j and Hernanz-Falc\'{o}n, Patricia and Gordon d and David l and Schweighoffer, Edina and Victor l and Reis e sousa, Caetano }, citeulike-article-id = {1363726}, doi = {10.1002/eji.200636830}, journal = {European Journal of Immunology}, keywords = {erk-il-10}, number = {6}, pages = {1600--1612}, posted-at = {2007-06-04 21:36:48}, priority = {2}, title = {Syk-dependent ERK activation regulates IL-2 and IL-10 production by DC stimulated with zymosan}, url = {http://dx.doi.org/10.1002/eji.200636830}, volume = {37}, year = {2007} }

TY - JOUR ID - citeulike:1363726 L3 - citeulike-article-id:1363726 TI - Syk-dependent ERK activation regulates IL-2 and IL-10 production by DC stimulated with zymosan JF - European Journal of Immunology VL - 37 IS - 6 SP - 1600 EP - 1612 AD - Immunobiology Laboratory, Cancer Research UK, London Research Institute, London, UK; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, USA; National Institute for Medical Research, London, UK; Department of Medicine, McMaster University, Hamilton, Ontario, Canada N2 - 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. KW - erk-il-10 AU - Emma c AU - Matthew j AU - Hernanz-Falcón, Patricia AU - Gordon d AU - David l AU - Schweighoffer, Edina AU - Victor l AU - Reis e sousa, Caetano PY - 2007/// UR - http://dx.doi.org/10.1002/eji.200636830 ER -