Signalling crosstalk between NOD2 and IL-31
Activation of appropriate CD4+ T helper cell responses is crucial in most infections caused by bacterial pathogens. However, acute Th2-mediated inflammation, which can occur coevally, may specifically suppress Th1-immunity. Here we hypothesise that the Th2 derived cytokine IL-31 may be a key factor in supporting immune reactions against NOD2-activating pathogens which invade an organism that is currently undergoing a severe Th2 inflammation. We speculate that, although pathogen-induced Th1-mediated immunity may be suppressed by type 2 specific cytokines like IL-4 and IL-13, IL-31, a novel Th2-derived cytokine, significantly contributes to clearance of the pathogen. We postulate that the crosstalk between IL-31- and NOD2-dependent signalling results in a synergistic activation of DCs, hallmarked by the production of numerous pro-inflammatory mediators which are consequentially capable of promoting the enhanced release of IL-17 and IFN-g from Th cells. DCs co-activated by IL-31 and a NOD2 ligand (e.g. MDP) may therefore strongly contribute to the manifestation of a Th17 phenotype and support clearance of the pathogen.

 This project is funded by the Austrian „Fond zur Förderung der Wissenschaftlichen Forschung“, Grant P25696.