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GSE4485
Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Global expression profiling of airway epithelial cells infected with Pseudomonas aeruginosa and the rsmA mutant.
Publication Title
Pseudomonas aeruginosa infection of airway epithelial cells modulates expression of Kruppel-like factors 2 and 6 via RsmA-mediated regulation of type III exoenzymes S and Y.
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa
- 6 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
LysR-type transcriptional regulators (LTTRs) are emerging as key circuit components in regulating microbial stress responses and are implicated in modulating oxidative stress in the human opportunistic pathogen Pseudomonas aeruginosa. The oxidative stress response encapsulates several strategies to overcome the deleterious effects of reactive oxygen species. However, many of the regulatory components and associated molecular mechanisms underpinning this key adaptive response remain to be characterised. Comparative analysis of publically available transcriptomic datasets led to the identification of a novel LTTR, PA2206, whose expression was altered in response to a range of host signals in addition to oxidative stress. PA2206 was found to be required for tolerance to H2O2 in vitro and lethality in vivo in the Zebrafish embryo model of infection. Transcriptomic analysis in the presence of H2O2 showed that PA2206 altered the expression of 58 genes, including a large repertoire of oxidative stress and iron responsive genes, independent of the master regulator of oxidative stress, OxyR. Contrary to the classic mechanism of LysR regulation, PA2206 did not autoregulate its own expression and did not influence expression of adjacent or divergently transcribed genes. The PA2214-15 operon was identified as a direct target of PA2206 with truncated promoter fragments revealing binding to the 5-ATTGCCTGGGGTTAT-3 LysR box adjacent to the predicted -35 region. PA2206 also interacted with the pvdS promoter suggesting a global dimension to the PA2206 regulon, and suggests PA2206 is an important regulatory component of P. aeruginosa adaptation during oxidative stress.
Publication Title
A non-classical LysR-type transcriptional regulator PA2206 is required for an effective oxidative stress response in Pseudomonas aeruginosa.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 49 Downloadable Samples
Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy.
Sample Metadata Fields
Sex, Age, Disease, Race
View Samples- Homo sapiens
- 39 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Infection with the human T lymphotropic virus type 1 (HTLV-1) remains asymptomatic in the majority of carriers; however, some 5% develop a chronic inflammation of the central nervous system termed HTLV-1-associated myelopathy (HAM). It is not well understood how the virus triggers the onset of HAM after many years of clinical latency and importantly, what distinguishes hosts who develop the disease from those who remain asymptomatic. In this study we tested the hypothesis that patients with HAM can be distinguished from asymptomatic HTLV-1 carriers (ACs) and uninfected subjects by their whole blood transcriptional profiles. Here, we compare unstimulated whole blood gene expression profiles of 20 asymptomatic HTLV-1 carriers (ACs), 10 patients with HAM and 9 uninfected healthy control subjects to (1) identify a transcriptional signature associated with presence of HAM and (2) identify cell types and pathways abnormally regulated in HAM by canonical and modular pathway analysis.
Publication Title
Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy.
Sample Metadata Fields
Sex, Age, Disease, Race
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Infection with the human T lymphotropic virus type 1 (HTLV-1) remains asymptomatic in the majority of carriers; however, some 5% develop a chronic inflammation of the central nervous system termed HTLV-1-associated myelopathy (HAM). It is not well understood how the virus triggers the onset of HAM after many years of clinical latency and importantly, what distinguishes hosts who develop the disease from those who remain asymptomatic. In a previous study we identified a 80-gene transcriptional signature of HAM based in the hypothesis that patients with HAM can be distinguished from asymptomatic HTLV-1 carriers (ACs) and uninfected subjects by their whole blood transcriptional profiles. In this study we wished to validate the 80-gene signature on an independent cohort comprising 17 asymptomatic HTLV-1 carriers (ACs), 10 patients with HAM and 8 uninfected healthy control subjects.
Publication Title
Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy.
Sample Metadata Fields
Sex, Age, Disease, Race
View Samples- Mus musculus
- 36 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Pattern recognition receptors (PRR) detect microbial products and induce cytokines which shape the immunological response. Interleukin-12 (IL-12), tumor necrosis factor alpha (TNF-) and IL-1 are proinflammatory cytokines which can be essential for resistance against infection, but if produced at high levels, may contribute to immunopathology. In contrast, IL-10 is an immunosuppressive cytokine which dampens proinflammatory responses, but can also lead to defective pathogen clearance. The regulation of these cytokines is therefore central to the generation of an effective but balanced immune response. Here, we show that macrophages derived from C57BL/6 mice produce low levels of IL-12, TNF- and IL-1, but high levels of IL-10 in response to TLR4 and TLR2 ligands LPS and PamCSK4, and Burkholderia pseudomallei a Gram-negative bacterium which activates TLR 2/4. In contrast, macrophages derived from BALB/c mice show a reciprocal pattern of cytokine production. Differential production of IL-10 in B. pseudomallei and LPS stimulated C57BL/6 and BALB/c macrophages was due to a type I IFN dependent, but IL-27 independent mechanism. Further, type I IFN contributed to differential IL-1 and IL-12 production in B. pseudomallei and LPS stimulated C57BL/6 and BALB/c macrophages, via both IL-10-dependent and independent mechanisms. These findings highlight key pathways responsible for the regulation of pro- and anti-inflammatory cytokines in macrophages and reveal how they may differ according to the genetic background of the host.
Publication Title
Differential Production of Type I IFN Determines the Reciprocal Levels of IL-10 and Proinflammatory Cytokines Produced by C57BL/6 and BALB/c Macrophages.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Mus musculus
- 192 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Listeriosis is an infectious disease caused by the intracellular bacterium Listeria monocytogenes. To control the infection effectively, the host immune response is directed by intercellular signalling molecules called cytokines that are produced by immune cells following sensing of the bacteria. In this study we used gene expression analysis to examine complex immune signalling networks in the blood and tissues of mice infected with L. monocytogenes. We show that a large set of genes are perturbed in both blood and tissue upon infection and that the transcriptional responses in both are enriched for pathways of the immune response. From these data we also observe an important signalling network emerge from a group of cytokines called interferons (IFNs). Previous findings suggest that different IFN family members can determine the balance between successful and impaired immune responses to L. monocytogenes and several other bacterial infections. Using mice deficient for the detrimental type I IFN signalling pathway we show that IFN-inducible genes are differentially regulated at different times upon infection but also present at much lower levels in uninfected mice highlighting how dysregulation of this network in the steady state may determine the outcome of this bacterial infection.
Publication Title
Analysis of Transcriptional Signatures in Response to Listeria monocytogenes Infection Reveals Temporal Changes That Result from Type I Interferon Signaling.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 62 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
TPL-2-ERK1/2 signaling promotes host resistance against intracellular bacterial infection by negative regulation of type I IFN production.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 61 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of Mtb infected murine macrophages derived from C57Bl/6 WT, TPL2KO, IFNARKO & TPL2IFNAR DKO mice [Set 2]
Publication Title
TPL-2-ERK1/2 signaling promotes host resistance against intracellular bacterial infection by negative regulation of type I IFN production.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of Mtb infected murine macrophages derived from C57Bl/6 WT, TPL2KO, IFNARKO & TPL2IFNAR DKO mice [Set 1]
Publication Title
TPL-2-ERK1/2 signaling promotes host resistance against intracellular bacterial infection by negative regulation of type I IFN production.
Sample Metadata Fields
Specimen part
View Samples