Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Modulation of mucosal immune responses to Clostridium difficile by peroxisome proliferator-activated receptor γ and microRNA-146b

ABSTRACT: BACKGROUND: miRNA have been shown to play an important role during immune-mediated diseases such as inflammatory bowel disease. The aim of this study was to assess differential expression of miRNA between uninfected and infected mice with Clostridium difficile strain VPI 10463 RESULTS: MicroRNA (miRNA)-sequencing analysis indicated that miR-146b, miR-1940, and miR-1298 were significantly overexpressed in colons of C. difficile-infected mice Colon of uninfected and C.difficile-infected C57BL6/J WT mice were sampled at day 4 post-infection with Clostridium difficile VPI 10463. The infection dose was 107 cfu/mouse.

ORGANISM(S): Mus musculus

SUBMITTER: Pawel Michalak

PROVIDER: E-GEOD-39235 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Modeling the role of peroxisome proliferator-activated receptor γ and microRNA-146 in mucosal immune responses to Clostridium difficile.

Viladomiu Monica M Hontecillas Raquel R Pedragosa Mireia M Carbo Adria A Hoops Stefan S Michalak Pawel P Michalak Katarzyna K Guerrant Richard L RL Roche James K JK Warren Cirle A CA Bassaganya-Riera Josep J

PloS one 20121011 10

Clostridium difficile is an anaerobic bacterium that has re-emerged as a facultative pathogen and can cause nosocomial diarrhea, colitis or even death. Peroxisome proliferator-activated receptor (PPAR) γ has been implicated in the prevention of inflammation in autoimmune and infectious diseases; however, its role in the immunoregulatory mechanisms modulating host responses to C. difficile and its toxins remains largely unknown. To characterize the role of PPARγ in C. difficile-associated disease ...[more]

PMID: 23071818

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Project description:Clostridium difficile is an anaerobic spore-forming rod-shaped gram-positive bacterium that can infect both humans and animals. Most studies on the pathogenesis of C. difficile have focused on its toxins and their effect on the host cells. Recently, we utilized microarrays to identify conserved and divergent genes associated with virulence in C. difficile isolates from humans and animals. Our data provided the first clue toward a complex mechanism underlying host adaptation and pathogenesis. Microarray technology offers an efficient high-throughput tool to study the transcriptional profiles of pathogens and infected host cells. Transcriptomes of C. difficile after exposure to environmental and antibiotic stresses and those of human epithelial colorectal Caco-2 cells upon TcdA treatment have been analyzed. To our knowledge, there are still no reports on the transcriptomic study of host-pathogen interactions for C. difficile infection (CDI). In vitro analyses of interplay between host and pathogen are essential to unravel the mechanisms of infection and to investigate the host response to infection. We therefore employed microarrays to study both bacterial and human cellular transcriptome kinetics during CDI to Caco-2 cells. Here we present a large-scale analysis of transcriptional profiles to reveal molecular determinants playing a role in C. difficile pathogenesis and the host response. We found that there were 254 and 224 differentially-expressed genes after CDI in C. difficile and Caco-2 cells, respectively. These genes are clustered according to their functional categories and their potential roles in pathogenesis and host response are discussed. Our results will not only increase our understanding on the host-pathogen interaction, but may also provide targets for drug development. Clostridium difficile: Control vs Infection (time course) mRNA with genomic DNA of tested and reference strains Caco-2 cells: Control vs Infected with Clostridium difficile Time-course experiments of Caco-2 cells infected with C. difficile for 30, 60 and 120 min

Project description:Clostridium difficile is a gram-positive, spore-forming enteric anaerobe which can infect humans and a wide variety of animal species. Recently, the incidence and severity of human C. difficile infection has markedly increased. In this study, we evaluated the genomic content of 73 C. difficile strains isolated from humans, horses, cattle, and pigs by comparative genomic hybridization with microarrays containing coding sequences from C. difficile strains 630 and QCD-32g58. The sequenced genome of C. difficile strain 630 was used as a reference to define a candidate core genome of C. difficile and to explore correlations between host origins and genetic diversity. Approximately 16% of the genes in strain 630 were highly conserved among all strains, representing the core complement of functional genes defining C. difficile. Absent or divergent genes in the tested strains were distributed across the entire C. difficile 630 genome and across all the predicted functional categories. Interestingly, certain genes were conserved among strains from a specific host species, but divergent in isolates with other host origins. This information provides insight into the genomic changes which might contribute to host adaptation. Due to a high degree of divergence among C. difficile strains, a core gene list from this study offers the first step toward the construction of diagnostic arrays for C. difficile.investigated by determining changes in transcript profiles when aerobic steady-state cultures were depleted of air. Dye-swap experiments with genomic DNA of tested and reference strains 8383cy3.gpr- Cy3 – test, Cy5 – reference 8384cy3.gpr- Cy3 – test, Cy5 – reference 8384cy5.gpr- Cy3 – reference, Cy5 – test 8385cy3.gpr- Cy3 – test, Cy5 – reference 8385cy5.gpr- Cy3 – reference, Cy5 – test 8386cy3.gpr- Cy3 – test, Cy5 – reference 8525cy3.gpr- Cy3 – test, Cy5 – reference 8525cy5.gpr- Cy3 – reference, Cy5 – test 8527cy5.gpr- Cy3 – reference, Cy5 – test 8529cy5.gpr- Cy3 – reference, Cy5 – test 8531cy3.gpr- Cy3 – test, Cy5 – reference 8531cy5.gpr- Cy3 – reference, Cy5 – test 8533cy3.gpr- Cy3 – test, Cy5 – reference 8533cy5.gpr- Cy3 – reference, Cy5 – test 8596cy3.gpr- Cy3 – test, Cy5 – reference 8596cy5.gpr- Cy3 – reference, Cy5 – test 8694cy3.gpr- Cy3 – test, Cy5 – reference 8694cy5.gpr- Cy3 – reference, Cy5 – test 2 GPR files per Sample record except for 4 Sample records (GSM480414, GSM480417, GSM480419, and GSM480420) which have 1 GPR file each 4 GPR file for those Sample records are lost

Dataset Information

Modulation of mucosal immune responses to Clostridium difficile by peroxisome proliferator-activated receptor γ and microRNA-146b

Publications

Modeling the role of peroxisome proliferator-activated receptor γ and microRNA-146 in mucosal immune responses to Clostridium difficile.

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