Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human dendritic cells treated with lipopolysaccharides and R848

ABSTRACT: Toll-like receptor (TLR) signalling activation by pathogens is critical to the induction of immune responses, and demands tight regulation. Chemokine ligand 2 (CCL2) secretion triggered by TLR4 or TLR8 engagement is strongly inhibited upon simultaneous activation of both TLRs in human monocyte-derived dendritic cells (MD-DC). Impaired CCL2 secretion occurs concomitantly to IL-12 up-regulation, being part of a complex regulatory circuit ensuring optimal Th type 1 polarization. Interestingly, triggering selected TLRs or their combinations differently affects nuclear factor-kB p65 activation and microRNA expression. To investigate in details such different modulation we performed a microarray profiling of MD-DCs stimulated by different TLRs agonist or their combination in three different donors. We found that CCL2 supplies an important immunomodulatory role to DCs, and may contribute to dictate the cytokine profile in Th type 1 responses induced by DCs.

ORGANISM(S): Homo sapiens

SUBMITTER: Andrea Masotti

PROVIDER: E-MEXP-2183 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

CC chemokine ligand 2 down-modulation by selected Toll-like receptor agonist combinations contributes to T helper 1 polarization in human dendritic cells.

Del Cornò Manuela M Michienzi Alessandro A Masotti Andrea A Da Sacco Letizia L Bottazzo Gian Franco GF Belardelli Filippo F Gessani Sandra S

Blood 20090522 4

Toll-like receptor (TLR) signaling activation by pathogens is critical to the induction of immune responses, and demands tight regulation. We describe in this study that CC chemokine ligand 2 (CCL2) secretion triggered by TLR4 or TLR8 engagement is strongly inhibited upon simultaneous activation of both TLRs in human monocyte-derived dendritic cells (DCs). Impaired CCL2 secretion occurs concomitantly to interleukin-12 up-regulation, being part of a complex regulatory circuit ensuring optimal T h ...[more]

PMID: 19465691

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Project description:Phenotypic plasticity, the ability of one genotype to express different phenotypes in response to changing environmental conditions, is one of the most common phenomena characterising the living world and is not only relevant for the ecology but also for the evolution of species. Daphnia, the waterflea, is a textbook example for predator induced phenotypic plastic defences including changes in life-history, behaviour and morphology. However, the analysis of molecular mechanisms underlying these inducible defences is still in its early stages. We exposed Daphnia magna to chemical cues of the predator Triops cancriformis to identify key processes underlying plastic defensive trait formation. D. magna is known to develop an array of morphological changes in the presence of T. cancriformis including changes of carapace morphology and cuticle hardening. To get a more comprehensive idea of this phenomenon, we studied four different genotypes originating from habitats with different predation history, reaching from predator-free to temporary habitats containing T. cancriformis. We analysed the morphologies as well as proteomes of predator-exposed and control animals. Three genotypes showed morphological changes when the predator was present. Using a high-throughput proteomics approach, we found 294 proteins which were significantly altered in their abundance after predator exposure in a general or genotype dependant manner. Proteins connected to genotype dependant responses were related to the cuticle, protein synthesis and calcium binding whereas the yolk protein vitellogenin increased in abundance in all genotypes, indicating their involvement in a more general response. Furthermore, genotype dependant responses at the proteome level correlated well with local adaptation to Triops predation. Altogether, our study provides new insights concerning genotype dependant and general molecular processes involved in predator-induced phenotypic plasticity in D. magna.

Dataset Information

Transcription profiling of human dendritic cells treated with lipopolysaccharides and R848

Publications

CC chemokine ligand 2 down-modulation by selected Toll-like receptor agonist combinations contributes to T helper 1 polarization in human dendritic cells.

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