Similar Datasets
Project description:Transcriptional profile of monocytes in the colon in response to C. rodentium infection
| PRJNA473531 | ENA
Project description:The identification of Atg16L1 as a susceptibility gene has implicated antibacterial autophagy in the pathogenesis of Crohn's disease, a major type of inflammatory bowel disease (IBD). However, the role of Atg16L1 during extracellular bacterial infections of the intestine has not been sufficiently examined and compared to the function of other IBD susceptibility genes such as Nod2. We now find that Atg16L1 mutant mice are extraordinarily resistant to intestinal disease induced by the model bacterial pathogen Citrobacter rodentium. We further demonstrate that Atg16L1 deficiency alters the intestinal environment to mediate an enhanced immune response that is dependent on monocytic cells, and that Atg16L1/Nod2 double mutant mice lose this advantage. These results reveal an unappreciated immuno-suppressive function of an IBD gene, and raise the possibility that gene variants that affect the autophagy pathway were evolutionarily maintained to protect against certain life-threatening infections. Twenty samples have been analyzed. All are colonic tissue from mice. Controls are uninfected WT mice, uninfected Atg16L1 mutant mice (Atg16L1HM) (n=3/genotype). Treatment conditions are tissue from WT and Atg16L1 mutant mice 6 days after C. rodentium infection (n=4/genotype) and 15 days after infection (n=3/genotype).
2013-11-27 | E-GEOD-49109 | biostudies-arrayexpress
Project description:Overall hypothesis: RNAseq can be used to examine and compare the vitamin A (VA) effect, Infection effect caused by Citrobacter rodentium (C. rodentium), and the Interaction effect (VA status × C. rodentium infection) in mouse small intestine (SI) and colon, on the scale of global transcriptome. Methods: Vitamin A deficient (VAD) mice were generated by feeding VAD diet to the pregnant C57/BL6 dams and their post-weaning offspring. Vitamin A sufficient (VAS) mice were fed with purified diet containing normal amount of VA. At weaning, mice were maintained on their respective diets and assigned to one of the four treatment groups (non-infected VAD, infected VAD, non-infected VAS and infected VAS) until the end of the experiments. For the infected groups, age-matched VAD or VAS mice were orally inoculated with C. rodentium. Mice during early (SI study) or peak (colon study) C. rodentium infection were euthanized in two separate studies. The SI study focused on SI and analyses were performed on samples collected 5 days post-infection. The colon study analyzed samples on post-infection day 10, the peak of C. rodentium infection. Total mRNA extracted from SI and colon were sequenced using Illumina HiSeq 2500 platform. Three to six biological replicates were sequenced in each group. Differentially Expressed Gene (DEG), Gene Ontology (GO) enrichment, and Weighted Gene Co-expression Network Analysis (WGCNA) were performed to characterize expression patterns and co-expression patterns. Results: a) differentially expression genes (DEGs) corresponding to VA effect were present in both the SI and colon. In SI, DEGs altered by VA were mainly involved in the retinoid metabolic pathway and immunity-related pathways. Novel target genes (e.g. Mbl2, Mmp9, Cxcl14, and Nr0b2) and cell types (based on Tuft cell and mast cell markers) under the regulation of VA were suggested by differential expression analysis coupled with the co-expression network analysis. In regard to the colon, VA demonstrated an overall suppressive effect on the cell division pathway. Finally, the comparison of co-expression modules between SI and colon indicated distinct regulatory networks in these two organs. b) In the SI, no Infection effect was detected during early infection, whereas in the colon, during peak of C. rodentium infection: 1) It has been shown that infection upregulated innate and adaptive immune functions, epithelial proliferation, apoptosis, endoplasmic reticulum stress, and reactive oxygen species production, as well as downregulated ion and water absorption. This helped to confirm the findings in previous studies, consolidating the knowledge-base about the host response to C. rodentium, 2) Pathways (e.g. neuron activity, smooth muscle contraction, vascular constriction, and developmental regulation) and additional ion transporters previously not known to be influenced by C. rodentium were suggested as potential mechanisms responsible for the diarrhea pathology and host response. 3) Retinoic acid receptor (RAR) and vitamin D receptor (VDR) signaling pathways appeared to be downregulated by infection, indicating that the malabsorption of micronutrients might be a danger signal for the host to switch from homeostasis to an anti-infection mode. c) In the SI, no Interaction (VA status × C. rodentium infection) effect was detected during early infection. In colon, 1329 genes corresponded to the Interaction effect. During the peak of C. rodentium infection, the sufficient stimulation of cell division, protein catabolism, apoptosis, transcription regulation, MHC class I, interferons, and cytokine signaling might be of key importance for the resistance of VAS mice. In addition, the proper maintenance of the proliferation, differentiation, migration, and activation of T cells and leukocytes during peak infection may also confer the VAS hosts with higher survival and clearance rate. On the other hand, our data suggested that the higher rate of lethal dehydration observed in infected VAD mice, may be attributed to the disrupted of HCO3- metabolism and an improperly high level of Cl- secretion. Conclusions: VA alters the gene expression profile in both SI and colon, whereas the Infection effect and the Interaction effect were only observed in colon during peak of C. rodentium infection, but not in the SI during early infection. Our studies suggest novel target genes and cell types under the regulation of VA in the SI, and indicate that the resistance of the VAS hosts may be attributed to the concordant control over ion/water absorption, immune functions, as well as the balance between epithelial hyperplasia and apoptosis.
2021-09-09 | GSE143290 | GEO
Project description:The intestinal epithelium is our first line of defense against infections of the gut and the plasticity in cellular differentiation of the intestinal epithelium is an important part of this response. Here we sequenced the colon intestinal epithelium from mice infected with Citrobacter rodentium to determine how the intestinal epithelium adapts in the context of an infection. By comparing these data to small intestinal organoids treated with cytokines (see related accessions) we determine that the intestinal epithelial response to C. rodentium infection correspond to a type III infection driven by IL22.
2022-05-08 | E-MTAB-9184 | biostudies-arrayexpress
Project description:The identification of Atg16L1 as a susceptibility gene has implicated antibacterial autophagy in the pathogenesis of Crohn's disease, a major type of inflammatory bowel disease (IBD). However, the role of Atg16L1 during extracellular bacterial infections of the intestine has not been sufficiently examined and compared to the function of other IBD susceptibility genes such as Nod2. We now find that Atg16L1 mutant mice are extraordinarily resistant to intestinal disease induced by the model bacterial pathogen Citrobacter rodentium. We further demonstrate that Atg16L1 deficiency alters the intestinal environment to mediate an enhanced immune response that is dependent on monocytic cells, and that Atg16L1/Nod2 double mutant mice lose this advantage. These results reveal an unappreciated immuno-suppressive function of an IBD gene, and raise the possibility that gene variants that affect the autophagy pathway were evolutionarily maintained to protect against certain life-threatening infections.
2013-11-27 | GSE49109 | GEO
Project description:Profiling of a total of 34,790 genes revealed a wide range of expression changes during the course of C. rodentium infection in murine colon. The majority of changes were observed during weeks 1 and 2, while relatively fewer changes were seen at week 3. Interestingly, chemokines made up 20% of the top twenty upregulated genes.
2009-07-01 | GSE16847 | GEO
Project description:To further understand immune mechanims involved in regulating intestinal inflammation, we employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential of regulating inflammation in the absence of IL-10. Whole colon tissue from IL-10-deficient and C57BL/6 (wild-type) mice was collected 2 weeks after Citrobacter rodentium infection and from uninfected controls. Consistent with the histological and cellular analysis, expression levels of many chemokines and cytokines involved in recruiting leukocytes and promoting inflammation were, on average, lower in IL-10 deficient compared to wild-type mice after infection. An exception to this general trend was IL-27, a cytokine with both pro- and anti-inflammatory properties. Two weeks after Citrobacter rodentium challenge, total RNA was extracted and analyzed from whole colon tissue of infected IL-10-deficient and wild-type mice, and compared to uninfected controls. Each sample contained equal amounts of total RNA from 4-5 female mice which were pooled and used in the experiment.
2014-03-12 | E-GEOD-55812 | biostudies-arrayexpress
Project description:We performed deep RNA sequencing and systematically analyzed the global gene expression profiles of C. rodentium-infected colon tissues from both susceptible and resistant congenic mice strains to determine the common transcriptomic responses to infection and the Rspo2-mediated dysregulated pathway signatures associated with the loss of disease tolerance.
2018-01-31 | GSE100546 | GEO
Project description:Opioids analgesics are frequently prescribed in the United States and worldwide. However, serious side effects such as addiction, immunosuppression and gastrointestinal symptoms limit their use. It has been recently demonstrated that morphine treatment results in significant disruption in gut barrier function leading to increased translocation of gut commensal bacteria. Further study indicated distinct alterations in the gut microbiome and metabolome following morphine treatment, contributing to the negative consequences associated with opioid use. However, it is unclear how opioids modulate gut homeostasis in the context of a hospital acquired bacterial infection. In the current study, a mouse model of C. rodentium infection was used to investigate the role of morphine in the modulation of gut homeostasis in the context of a hospital acquired bacterial infection. Citrobacter rodentium is a natural mouse pathogen that models intestinal infection by enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) and causes attaching and effacing lesions and colonic hyperplasia. Morphine treatment resulted in 1) the promotion of C. rodentium systemic dissemination, 2) increase in virulence factors expression with C. rodentium colonization in intestinal contents, 3) altered gut microbiome, 4) damaged integrity of gut epithelial barrier function, 5) inhibition of C. rodentium-induced increase in goblet cells, and 6) dysregulated IL-17A immune response. This is the first study to demonstrate that morphine promotes pathogen dissemination in the context of intestinal C. rodentium infection, indicating morphine modulates virulence factor-mediated adhesion of pathogenic bacteria and induces disruption of mucosal host defense during C. rodentium intestinal infection in mice. This study demonstrates and further validates a positive correlation between opioid drug use/abuse and increased risk of infections, suggesting over-prescription of opioids may increase the risk in the emergence of pathogenic strains and should be used cautiously. Therapeutics directed at maintaining gut homeostasis during opioid use may reduce the comorbidities associated with opioid use for pain management.
2020-02-18 | E-MTAB-7503 | biostudies-arrayexpress
Project description:We previously reported that hypusination in myeloid cells is required to limit the development of pathogenic bacteria in the gastrointestinal tract, including Helicobacter pylori for the stomach and C. rodentium in the colon. The aim of the present study was to investigate the role of epithelial hypusination on C. rodentium pathogenicity
2024-04-08 | GSE262899 | GEO