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GSE57008
Mus musculus
28 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Background: Influenza A virus (IAV) infections periodically cause substantial morbidity and mortality in the human population. In the lung, the primary targets for IAV replication are type II alveolar epithelial cells (AECII), which are increasingly recognized for their immunological potential. However, our knowledge of the role of AECII in anti-IAV immunity is incomplete and their in vivo response to infection has not been evaluated. To increase our understanding of their role in host-response to IAV-infection, we analyzed transcriptional regulation in primary AECII isolated from infected mice. Results: Microarray analyses of AECII isolated on the first three days following IAV-infection revealed extensive transcriptional regulation. A multitude of differentially expressed transcripts was identified and in comparison to whole-lung tissue revealed a strong contribution of AECII to respiratory anti-IAV responses. Type I interferon played a major role in the detected gene expression profile and functional pathway analyses showed AECII to be highly active in pathogen recognition, cell recruitment and antigen-presentation. Analysis of Toll-like receptor 7 (TLR7) deficient mice indicated AECII to rely on the hosts expression of this innate IAV-sensor to elicit their full response. Importantly, the AECII transcriptional profiles correlated to cell recruitment and type I interferon levels detected in the lungs of infected animals. Conclusions: Ex vivo analysis of primary murine AECII proved as a powerful tool to increase our understanding of AECII biology in infection. Our analysis revealed an exceptionally strong contribution of AECII to local host defenses by integrating signals provided by surrounding cells and direct pathogen recognition.
Publication Title
Alveolar Type II Epithelial Cells Contribute to the Anti-Influenza A Virus Response in the Lung by Integrating Pathogen- and Microenvironment-Derived Signals.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Chronic obstructive pulmonary disease (COPD) is a heterogenous respiratory disease mainly caused by smoking. Respiratory infections constitute a major risk factor for acute worsening of COPD symptoms or COPD exacerbation. Mitochondrial functionality, which is crucial for the execution of physiologic functions of metabolically active cells, is impaired in airway epithelial cells (AECs) of COPD patients as well as smokers. However, the potential contribution of mitochondrial dysfunction in AECs to progression of COPD, infection-triggered exacerbations in AECs and a potential mechanistic link between mitochondrial and epithelial barrier dysfunction is unknown to date. In this study, we used an in vitro COPD exacerbation model based on AECs exposed to cigarette smoke extract (CSE) followed by infection with Streptococcus pneumoniae (Sp). The levels of oxidative stress, as an indicator of mitochondrial stress were quantified upon CSE and Sp. The expression of proteins associated with mitophagy, mitochondrial content and biogenesis as well as mitochondrial fission and fusion was quantified upon CSE and Sp. Transcriptional AEC profiling was performed to identify the potential changes in innate immune pathways and correlate them with mitochondrial function. We found that CSE exposure substantially altered mitochondrial function in AECs by suppressing mitochondrial complex protein levels, reducing mitochondrial membrane potential and increasing mitochondrial stress and mitophagy. Moreover, CSE-induced mitochondrial dysfunction correlated with reduced enrichment of genes involved in apical junctions and innate immune responses to Sp, particularly type I interferon responses. Together, our results demonstrated that CSE-induced mitochondrial dysfunction may contribute to impaired innate immune responses to Sp and may thus trigger COPD exacerbation.
Publication Title
Cigarette Smoke Extract Disturbs Mitochondria-Regulated Airway Epithelial Cell Responses to Pneumococci.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The respiratory tract is constantly exposed to the environment and displays a favorable niche for colonizing microorganisms. However, the effects of respiratory bacterial carriage on the immune system and its implications for secondary responses remain largely unclear. We have employed respiratory carriage with Bordetella bronchiseptica (Bb) as the underlying model to comprehensively address effects on subsequent immune responses. Persistent carriage was associated with the stimulation of Bordetella-specific CD4+, CD8+ and CD4+CD25+Foxp3+ T cell responses and broad transcriptional activation was observed in CD4+CD25+ T cells. Importantly, transfer of lymphocytes from persistent carriers to acutely B. bronchiseptica infected mice resulted in a significantly increased bacterial burden in the recipients upper respiratory tract. In contrast, we found that B. bronchiseptica carriage resulted in a significant benefit for the host in systemic infection with Listeria monocytogenes. At the same time, vaccination and influenza A virus infection were unaffected. These data demonstrate that there are significant immune modulatory processes triggered by persistent B. bronchiseptica carriage that differentially affect subsequent immune responses. Thereby our results demonstrate the complexity of immune regulation induced by persistent bacterial carriage in the respiratory tract that can be beneficial or detrimental to the host, depending on the pathogen and the considered compartment.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
ChIP-on-chip analysis identifies IL-22 as direct target gene of ectopically expressed FOXP3 transcription factor in human T cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Noncommunicable chronic respiratory diseases (CRDs) such as chronic obstructive pulmonary disease (COPD) and asthma affect hundreds of millions of people and are associated with increasing morbidity and mortality. CRDs are multifactorial disorders and despite different etiologies they commonly manifest in pulmonary structural (airway remodeling, emphysema) and/or functional changes. In this study we used mice intrinsically developing autoimmune-mediated lung inflammation associated with lung pathology and immune imprinting partly comparable to hallmarks of CRD. The so called SPC-HAxTCR-HA transgenic mice (BALB/c genetic background), express a neo-self antigen (influenza A virus hemagglutinin, HA) on lung alveolar epithelial type II cells in the presence of HA-specific CD4+ T cells leading to the establishment of chronic lung inflammation. In order to characterize the inflammatory lung milieu of SPC-HAxTCR-HA mice in comparison to SPC-HA control mice (lacking HA-specific CD4+ T cells), we performed whole lung tissue transcriptional analyses (n = 3 / group). 378 transcripts were found to be differentially expressed in SPC-HAxTCR-HA lungs. 326 of those were up-regulated and 52 were down-regulated compared to SPC-HA control mice.
Publication Title
Chronic lung inflammation primes humoral immunity and augments antipneumococcal resistance.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The transcription factor (TF) Forkhead Box P3 (FOXP3) is constitutively expressed in high levels in natural occurring CD4+CD25+ regulatory T cells (nTreg) and is not only the most accepted marker for that cell population, but is considered lineage determinative. Chromatin immunoprecipitation (ChIP) of transcription factors in combination with genomic tiling microarray analysis (ChIP-on-Chip) has been shown to be an appropriate tool to identify FOXP3 transcription factor binding sites (TFBS) on a genome-wide scale. In combination with microarray expression analysis the ChIP-on-Chip technique allows to identify direct FOXP3 target genes. This dataset shows expression data of resting and mitogen stimulated (PMA / ionomycin) retrovirally transduced Jurkat T cells either expressing FOXP3(2) (J-FOXP3) or an empty vector control (J-GFP).
Publication Title
ChIP-on-chip analysis identifies IL-22 as direct target gene of ectopically expressed FOXP3 transcription factor in human T cells.
Sample Metadata Fields
Cell line
View Samples- Saccharomyces cerevisiae
- 32 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Fungal group III histidine kinases are the molecular targets of some classes of fungicides. In contrast to the yeast Saccharomyces cerevisiae, the fungal pathogen Candida albicans possesses a group III histidine kinase, CaNik1p, also called Cos1p. To investigate the function of CaNIK1, the gene was expressed in S. cerevisiae. The transformants became susceptible to antifungal compounds to which the wild-type strain is resistant. The susceptibility was related to the activation of the MAP kinase Hog1p of the osmotic stress response pathway. Gene expression analysis revealed a strong overlap of the responses to osmotic stress and to fludioxonil at early time points. While the response to fludioxonil persisted, the response to osmotic stress was diminished with time.
Publication Title
No associated publication
Sample Metadata Fields
Treatment
View Samples- Pseudomonas aeruginosa
- 30 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Pseudomonas aeruginosa is a threatening, opportunistic pathogen causing disease in immunocompromised individuals. The hallmark of P. aeruginosa virulence is its multi-factorial and combinatorial nature. It renders such bacteria infectious for many organisms and it is often resistant to antibiotics. To gain insights into the physiology of P. aeruginosa during infection, we assessed the transcriptional programs of three different P. aeruginosa strains directly after isolation from burn wounds of humans. We compared the programs to those of the same strains using two infection models: a plant model, which consisted of the infection of the midrib of lettuce leaves, and a murine tumor model, which was obtained by infection of mice with an induced tumor in the abdomen. All control conditions of P. aeruginosa cells growing in suspension and as a biofilm were added to the analysis. We found that these different P. aeruginosa strains express a pool of distinct genetic traits that are activated under particular infection conditions regardless of their genetic variability. The knowledge herein generated will advance our understanding of P. aeruginosa virulence and provide valuable cues for the definition of prospective targets to develop novel intervention strategies.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa
- 26 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
The opportunistic bacterium Pseudomonas aeruginosa is a major nosocomial pathogen causing both devastating acute and chronic persistent infections. During the course of an infection, P.aeruginosa rapidly adapts to the specific conditions within the host. In the present study, we aimed at the identification of genes that are highly expressed during biofilm infections such as in chronically infected lungs of patients with cystic fibrosis (CF), burn wounds and subcutaneous mouse tumours. We found a common subset of differentially regulated genes in all three in vivo habitats and evaluated whether their inactivation impacts on the bacterial capability to form biofilms in vitro and to establish biofilm-associated infections in a murine model. Additive effects on biofilm formation and host colonization were discovered by the combined inactivation of several highly expressed genes. However, even combined inactivation was not sufficient to abolish the establishment of an infection completely. These findings can be interpreted as evidence that either redundant traits encode functions that are essential for in vivo survival and chronic biofilm infections and/or bacterial adaptation is considerably achieved independently of transcription levels. Supplemental screens, will have to be applied in order to identify the minimal set of key genes essential for the establishment of chronic infectious diseases.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa
- 4 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Many Gram-negative bacteria employ cell-to-cell communication mediated by N-acyl homoserine lactones (quorum sensing) to control expression of a wide range of genes including, but not limited to, genes encoding virulence factors. Outside the laboratory, the bacteria live in complex communities where signals may be perceived across species. We here present a newly found natural quorum sensing inhibitor, produced by the pseudomonads Pseudomonas sp. B13 and Pseudomonas reinekei MT1 as a blind end in the biodegradation of organochloride xenobiotics, which inhibits quorum sensing in P.aeruginosa in naturally occurring concentrations. This catabolite, 4-methylenebut-2-en-4-olide, also known as protoanemonin, has been reported to possess antibacterial properties, but seems to have dual functions. Using transcriptomics and proteomics, we found that protoanemonin significantly reduced expression of genes and secretion of proteins known to be under control of quorum sensing in P.aeruginosa. Moreover, we found activation of genes and gene products involved in iron starvation response. It is thus likely that inhibition of quorum sensing, as the production of antibiotics, is a phenomenon found in complex bacterial communities.
Publication Title
Protoanemonin: a natural quorum sensing inhibitor that selectively activates iron starvation response.
Sample Metadata Fields
Compound
View Samples