Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/99524
Title: Synergism between Curdlan and GM-CSF confers a strong inflammatory signature to Dendritic cells
Authors: Min, Lin
Siti Aminah Mohammad Isa
Fam, Wee Nih
Sze, Siu Kwan
Beretta, Ottavio
Mortellaro, Alessandra
Ruedl, Christiane
Issue Date: 2012
Source: Min, L., Siti, A. M. I., Fam, W. N., Sze, S. K., Beretta, O., Mortellaro, A.,& Ruedl, C. (2012). Synergism between Curdlan and GM-CSF confers a strong inflammatory signature to Dendritic cells. The journal of immunology, 188(4), 1789-1798.
Series/Report no.: The journal of immunology
Abstract: A simultaneous engagement of different pathogen recognition receptors provides a tailor-made adaptive immunity for an efficient defense against distinct pathogens. For example, cross-talk of TLR and C-type lectin signaling effectively shapes distinct gene expression patterns by integrating the signals at the level of NF-κB. In this study, we extend this principle to a strong synergism between the dectin-1 agonist curdlan and an inflammatory growth factor, GM-CSF. Both together act in synergy in inducing a strong inflammatory signature that converts immature dendritic cells (DCs) to potent effector DCs. A variety of cytokines (IL- 1β, IL-6, TNF-α, IL-2, and IL-12p70), costimulatory molecules (CD80, CD86, CD40, and CD70), chemokines (CXCL1, CXCL2, CXCL3, CCL12, CCL17), as well as receptors and molecules involved in fugal recognition and immunity such as Mincle, dectin-1, dectin-2, and pentraxin 3 are strongly upregulated in DC treated simultaneously with curdlan and GM-CSF. The synergistic effect of both stimuli resulted in strong IkBa phosphorylation, its rapid degradation, and enhanced nuclear translocation of all NF-κB subunits. We further identified MAPK ERK as one possible integration site of both signals, because its phosphorylation was clearly augmented when curdlan was coapplied with GM-CSF. Our data demonstrate that the immunomodulatory activity of curdlan requires an additional signal provided by GM-CSF to successfully initiate a robust β-glucan-specific cytokine and chemokine response. The integration of both signals clearly prime and tailor a more effective innate and adaptive response against invading microbes and fungi.
URI: https://hdl.handle.net/10356/99524
http://hdl.handle.net/10220/12908
DOI: http://dx.doi.org/10.4049/jimmunol.1101755
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

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