title: Synergism of NOD2 and NLRP3 activators promotes a unique transcriptional profile in murine dendritic cells.
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.
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
authors.forename: Cristina
authors.initials: C
authors.lastname: Conforti-Andreoni
authors.forename: Ottavio
authors.initials: O
authors.lastname: Beretta
authors.forename: Ginevra
authors.initials: G
authors.lastname: Licandro
authors.forename: Hong Liang
authors.initials: HL
authors.lastname: Qian
authors.forename: Matteo
authors.initials: M
authors.lastname: Urbano
authors.forename: Federico
authors.initials: F
authors.lastname: Vitulli
authors.forename: Paola
authors.initials: P
authors.lastname: Ricciardi-Castagnoli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mortellaro
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000818:Animals; D051928:CD47 Antigen / Q000235:genetics; D002352:Carrier Proteins / Q000502:physiology*; D016207:Cytokines / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism*; D004357:Drug Synergism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D016023:Integrins / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D053473:Nod2 Signaling Adaptor Protein / Q000502:physiology*; D015398:Signal Transduction; D014527:Uric Acid / Q000494:pharmacology
chemical_list: D051928:CD47 Antigen; D002352:Carrier Proteins; C497895:Cd47 protein, mouse; D016207:Cytokines; D016023:Integrins; D007376:Interleukin-2; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D014527:Uric Acid; D000119:Acetylmuramyl-Alanyl-Isoglutamine