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. 2010 Dec;88(6):1207-16.
doi: 10.1189/jlb.1009652. Epub 2010 Sep 30.

Synergism of NOD2 and NLRP3 activators promotes a unique transcriptional profile in murine dendritic cells

Cristina Conforti-Andreoni  1 , Ottavio Beretta, Ginevra Licandro, Hong Liang Qian, Matteo Urbano, Federico Vitulli, Paola Ricciardi-Castagnoli, Alessandra Mortellaro
Affiliations

Synergism of NOD2 and NLRP3 activators promotes a unique transcriptional profile in murine dendritic cells

Cristina Conforti-Andreoni et al. J Leukoc Biol. 2010 Dec.

Abstract

NLRs are cytoplasmic proteins that sense cellular stress and intracellular damage resulting from pathogen uptake. To date, the role of NLRs has been studied using combinations of NLR and TLR agonists, but the interplay between two different NLRs remains uncharacterized. In this study, we employed microarrays to investigate in DCs the regulation of gene transcription mediated by activation of NOD2 and NLRP3 pathways using MDP and MSU. MDP and MSU co-stimulation of murine BMDCs up-regulated the expression of genes encoding molecules for antigen presentation and co-stimulation (MHC class II, CD80, CD86), integrins (ITGB3, ITGAV), cytokines (IL-1α, IL-1β, IL-6, IL-2, IL-23p19, IL-12p40), and chemokines (CXCL1, CXCL2). Transcription of the cytokine genes induced by MDP and MSU partially depended on NOD2 but was independent of NLRP3. Finally, we showed that ERK1 and c-JUN activation increased upon MDP and MSU co-stimulation. As a whole, the results indicate that two different NLR activators synergize at the transcriptional level, leading to unique differential expression of genes involved in the innate immune response.

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