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-B. 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-1, IL-6, TNF-, 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 IKB phosphorylation, in its rapid degradation and in enhanced nuclear translocation of all NF-B 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 -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.
Synergism between curdlan and GM-CSF confers a strong inflammatory signature to dendritic cells.
Specimen part
View SamplesCalcineurin/NFAT/IL-2 signaling pathway is activated in dendritic cells (DC) upon encounter of glucan, the main component of the fungal cell wall, raising the question about the role of NFAT-regulated genes in DC biology in vivo. To directly assess the function of IL-2 secreted by DC, we analyzed mice lacking of IL-2 in the DC lineage, CD4-expressing cells and with complete deletion of IL-2 in the germ line in a mouse model of pulmonary fungal infection. Here we found that specifically the loss of IL-2 in DC resulted in increased mice mortality upon the fungus Aspergillus fumigatus challenge and expansion of Th17 cells in the lung. We demonstrated that only CD103+DC were able to release IL-2 in acute phase of pulmonary Aspergillosis through the Ca2+-Calcineurin-NFAT signaling. We also found that NFAT mediates IL-23 transcription in lung DC, where IL-2 results essential in restraining the priming of a pathogenic infiltrating IL-17+Sca1+CD90+CD4+ cell with stem cell like properties. Thus, IL-2 and IL-23 secreted by DC in the lung have an antagonistic relationship on the Th17 differentiation program with IL-2 inducing T cell differentiation and IL-23 inducing a stem cell like molecular signature to Th17 cells upon Aspergillus challenge. DC-Il2-/- then confer the Th17 stemness, releasing IL-23 in response to the fungus contributing to the development of a Th17 cell effector population, particularly pathogenic in infection.
CD103(+) Dendritic Cells Control Th17 Cell Function in the Lung.
Cell line, Treatment
View Samplesp53 is critically important in preventing oncogenesis but its role in non-cancer biology remains unclear. Macrophages exist as two subtypes (M1 and M2). Nutlin-3a (p53 activator) inhibits M2 gene expression and phenotype. p53 acts by suppressing transcription of c-Myc and thence regulates expression of a subset of M2 markers. This work has implications for our understanding of the mechanisms that regulate plasticity of macrophages in health and disease.
A unique role for p53 in the regulation of M2 macrophage polarization.
Specimen part, Treatment
View SamplesPseudomonas fluorescens strain SS101 (Pf.SS101) promotes growth of Arabidopsis thaliana, enhances greening and lateral root formation, and induces systemic resistance (ISR) against the bacterial pathogen Pseudomonas syringae pv. tomato (Pst). Here, targeted and untargeted approaches were adopted to identify bacterial determinants and underlying mechanisms involved in plant growth promotion and ISR by Pf.SS101. Based on targeted analyses, no evidence was found for volatiles, lipopeptides and siderophores in plant growth promotion by Pf.SS101. Untargeted, genome-wide analyses of 7,488 random transposon mutants of Pf.SS101 led to the identification of 21 mutants defective in both plant growth promotion and ISR. Many of these mutants, however, were auxotrophic and impaired in root colonization. Genetic analysis of three mutants followed by site-directed mutagenesis, genetic complementation and plant bioassays revealed the involvement of the phosphogluconate dehydratase gene edd, the response regulator gene colR and the adenylsulfate reductase gene cysH in both plant growth promotion and ISR. Subsequent comparative plant transcriptomics analyses strongly suggest that modulation of sulfur assimilation, auxin biosynthesis and transport, steroid biosynthesis and carbohydrate metabolism in Arabidopsis are key mechanisms linked to growth promotion and ISR by Pf.SS101.
Genome-wide analysis of bacterial determinants of plant growth promotion and induced systemic resistance by Pseudomonas fluorescens.
Specimen part, Treatment
View SamplesExperimental design: 1 genotype: PI- (resistant USDA Plant Introduction (PI462312) line containing SBR Rpp3 resistance gene) 3 treatments: Virulent soybean rust (Phakopsora pachyrhizi Tw80-2) challenge, avirulent soybean rust challenge (Hw94-1) & mock infection 3 replications 6 time points: 12, 24, 72, 144, 216 and 288 hours after inoculation TOTAL: 54 Affymetrix GeneChip(R) Soybean Genome Arrays Mock treatment: 0.01% Tween 20 Hawaii 94 treatment: 500,000 spores per ml in 0.01% Tween 20 Taiwan 80-2 treatment: 500,000 spores per ml in 0.01% Tween 20 ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Martijn van de Mortel (for Steve Whitham). The equivalent experiment is GM36 at PLEXdb.]
Biphasic gene expression changes elicited by Phakopsora pachyrhizi in soybean correlate with fungal penetration and haustoria formation.
Specimen part, Time
View SamplesExperimental design: 2 genotypes: PI230970 (resistant USDA Plant Introduction (PI) line containing SBR Rpp2 resistance gene) & Embrapa-48 (susceptible Brazilian cultivar) 2 treatments: Soybean rust challenge & mock infection 3 replications 10 time points: 6, 12, 18, 24, 36, 48, 72, 96, 120, 168hai TOTAL: 120 Affymetrix GeneChip(R) Soybean Genome Arrays ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Martijn van de Mortel. The equivalent experiment is GM2 at PLEXdb.]
Distinct biphasic mRNA changes in response to Asian soybean rust infection.
Specimen part, Time
View SamplesMutations in PROP1 are the most common cause of hypopituitarism in humans; therefore, unraveling its mechanism of action is highly relevant from a therapeutic perspective. Our current understanding of the role of PROP1 in the pituitary gland is limited to the regulation of pituitary transcription factors Hesx1 and Pit1. To elucidate the comprehensive PROP1-dependent gene regulatory network, we conducted genome wide analysis of PROP1 DNA binding and effects on gene expression in mutant tissues, isolated stem cells and engineered cell lines. We determined that PROP1 is essential for maintaining proliferation of stem cells and stimulating them to undergo an epithelial to mesenchymal transition-like process necessary for cell migration and differentiation. Genomic profiling reveals that PROP1 binds to and represses claudin 23, characteristic of epithelial cells, and it activates EMT inducer genes: Zeb2, Notch2 and Gli2. Our findings identify PROP1 as a central transcriptional component of pituitary stem cell differentiation. Overall design: Pituitary Colony forming cells mRNA of 13-day old wild type (Prop1 +/+), Prop1 mutants (Prop1df/df), wild type (Pit1+/+) and Pit1 mutants (Pit1 dw/dw) mice were generated by deep sequencing, in triplicates.
PROP1 triggers epithelial-mesenchymal transition-like process in pituitary stem cells.
Specimen part, Cell line, Subject
View SamplesThyroid hormones, thyroxine and triiodothyronine (T3) are crucial for cerebral cortex development acting through regulation of gene expression. To define the transcriptional program under T3 regulation we have performed RNA-Seq of T3-treated and untreated primary mouse cerebrocortical cells. The expression of 1,145 genes or 7.7% of expressed genes was changed upon T3 addition, of which 371 responded to T3 in the presence of cycloheximide indicating direct transcriptional regulation. The results were compared with available transcriptomic datasets of defined cellular types. In this way we could identify genomic targets of T3 in astrocytes and neurons, and in neuron subtypes, such as layer-specific neurons, and neurons expressing specific markers such as prepronociceptin, cholecystokinin, or cortistatin. T3 up-regulates mostly genes related to cell membrane events, such as G-protein signaling, neurotransmission, and ion transport, and down-regulates genes involved in nuclear events, such as cell division, M phase of cell cycle, and chromosome organization and segregation. Remarkably the transcriptomic changes induced by T3 sustain the transition from embryonic to adult patterns of gene expression. The results allowed us to define in molecular terms the elusive role of thyroid hormones on neocortical development. Overall design: Pregnant dams were euthanized on gestational day 17.5, and the fetuses were extracted and euthanized by decapitation. The cerebral cortices were dissected, disaggregated and finally the cells were suspended in culture medium. After 9 days incubation cells were incubated for 24 hours before adding T3 at a final concentration of 10 nM. The cells were harvested 24 hours later. Cells without T3 were incubated in parallel. Cerebral cortices from individual fetuses originated two replicas for the cell culture, one with T3 and another without T3. Number of samples: 6.
Global Transcriptome Analysis of Primary Cerebrocortical Cells: Identification of Genes Regulated by Triiodothyronine in Specific Cell Types.
No sample metadata fields
View SamplesT-cell clones were obtained by limiting dilution culture of PBMC of HTLV-1 carriers. Exon expression profiling was performed using Affymetrix exon array (Affymetrix Human Exon 1.0 ST Array) according to the manufacturer's instructions. Gene version of CEL files 01 to 12 are presented in GSE46518.
HTLV-1-infected CD4+ T-cells display alternative exon usages that culminate in adult T-cell leukemia.
Specimen part
View SamplesBackground: Extended hepatectomies may result in post-hepatectomy liver failure, a condition with a high mortality. The main purpose of the present study was to investigate and compare the gene expression profiles in rats subjected to increasing size of partial hepatectomy.
Gene Expression in the Liver Remnant Is Significantly Affected by the Size of Partial Hepatectomy: An Experimental Rat Study.
Specimen part, Treatment
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