Synergism between curdlan and GM-CSF in mouse dendritic cells

ABSTRACT: A simultaneous engagement of different pathogen recognition receptors provides a tailor made adaptive immunity for an efficient defence against distinct pathogens. For example, cross talk of TLR and c-type lectin signalling effectively shapes distinct gene expression patterns by integrating the signals at the level of NF-κB. Here, 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 which converts immature 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 up-regulated in DC treated simultaneously with curdlan and GM-CSF. The synergistic effect of both stimuli resulted in strong IKBα phosphorylation, in its rapid degradation and in enhanced nuclear translocation of all NF-κB subunits. We further identified MAPK ERK, as one possible integration site of both signals, since its phosphorylation was clearly augmented when curdlan was co-applied 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. CD11b+ fraction of FLT3L generated BM DCs (3-4 x106) were stimulated for 4 hours with 100 or 1 μg/ml curdlan in presence or absence of 5 ng/ml GM-CSF in triplicates.

ORGANISM(S): Mus musculus

SUBMITTER: Michael Poidinger 

PROVIDER: E-GEOD-32986 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress