Ontology highlight
ABSTRACT:
PROVIDER: PRJNA967825 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24460500_1.fastq.gz | Fastqsanger.gz | |||
| SRR24460500_2.fastq.gz | Fastqsanger.gz | |||
| SRR24460501_1.fastq.gz | Fastqsanger.gz | |||
| SRR24460501_2.fastq.gz | Fastqsanger.gz | |||
| SRR24460502_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 48 |
Similar Datasets
Project description:Colonic goblet cells respond to invading enteropathogens by secreting Muc2 mucin and other specific goblet cell proteins that physically entrap and expel microbes away from the epithelium. At present, it is unclear how innate effectors in the gut, including small cationic cathelicidin peptides secreted by the intestinal epithelium and leukocytes, contribute to mucus barrier defense during infections. In this study, we used cathelicidin-deficient (Camp-/-) mice, colonoids, and human colonic LS174T goblet cells to elucidate the mechanisms by which cathelicidin regulates goblet cell secretions in innate host defense against attaching/effacing Citrobacter rodentium. We showed that even though Camp-/- littermates infected with C. rodentium displayed increased fecal shedding and epithelial colonization, Muc2 mucin granules were retained in bloated colonic goblet cells that impaired mucus secretion and expressed less mucus-associated proteins, as quantified by proteomic analysis. C. rodentium infected Camp-/- littermates showed impaired reactive oxygen species (ROS) production and transcriptomic profiling associated with decreased ROS biosynthesis and an increase in ROS negative regulators. Camp-/- bone marrow derived macrophages produced less ROS than their wild-type counterparts. In LS174T goblet cells, human cathelicidin LL-37 promptly induced the secretion of goblet cell-associated TFF3 and RELMβ, which was dependent on ROS production. These findings demonstrate that cathelicidin signaling in colonic goblet cells regulates mucus and mucin-associated protein secretion via an ROS-dependent mechanism to clear bacterial infections and restore gut homeostasis.
2023-05-04 | PXD041957 | Pride
Project description:Mucus produced by goblet cells in the gastrointestinal (GI) tract forms a biological barrier that protects the intestine from invasion by commensals and pathogens. However, the host-derived regulatory network that controls mucus secretion and thereby changing gut microbiota has not been well studied. We found Forkhead box protein O1 (Foxo1) regulates mucus secretion by goblet cells and determines intestinal homeostasis. Loss of Foxo1 in intestinal epithelial cells (IECs) results in a defect in goblet cell autophagy and mucus secretion, leading to impaired gut microenvironment and dysbiosis.
2021-06-23 | GSE178650 | GEO
Project description:Background; MUC2 mucin produced by intestinal goblet cells is the major component of the intestinal mucus barrier. MUC2 homo-oligomerizes intracellularly into large secreted polymers which give mucus its viscous properties. The inflammatory bowel disease (IBD) ulcerative colitis is characterized by depleted goblet cells and a reduced mucus layer, whereas goblet cells and the mucus layer are increased in the other major inflammatory bowel disease, Crohnâs disease. Methods and Findings; By murine N-ethyl-N-nitrosourea-mutagenesis we identified two distinct non-complementing missense mutations in Muc2 exons encoding N- and C-terminal homo-oligomerization domains causing an ulcerative colitis-like phenotype. Both strains developed mild spontaneous distal intestinal inflammation, chronic diarrhea, rectal bleeding and prolapse, increased susceptibility to acute and chronic colitis induced by a luminal toxin, aberrant Muc2 biosynthesis, smaller goblet cell thecae (less stored mucin) and a diminished mucus barrier. Enhanced local production of IL-1beta, TNF-alpha and IFN-gamma was seen in the distal colon. The number of leukocytes within mesenteric lymph nodes was increased five-fold and leukocytes cultured in vitro produced both Th1 and Th2 cytokines (IFN-gamma, TNF-alpha and IL-13). Intestinal permeability was increased and the luminal bacterial flora were more heavily coated with immunoglobulin as occurs in IBD. This pathology was accompanied by accumulation of the Muc2 precursor and ultrastructural and biochemical evidence of endoplasmic reticulum (ER) stress in goblet cells, activation of the unfolded protein response, and altered intestinal expression of genes involved in ER stress, inflammation, apoptosis and wound repair. Expression of mutated Muc2 oligomerization domains in vitro demonstrated that aberrant Muc2 oligomerization underlies the ER stress. These models show that mutations in Muc2 oligomerization domains can lead to aberrant assembly of the Muc2 complex leading to ER stress, a depleted mucus barrier and intestinal inflammation. In ulcerative colitis we demonstrate similar accumulation of non-glycosylated MUC2 precursor in goblet cells together with ultrastructural and biochemical evidence of ER stress even in non-inflamed intestinal tissue. Conclusions; The observations that mucin misfolding and ER stress lead directly to intestinal inflammation and that ER stress and goblet cell pathology occur in ulcerative colitis suggest that ER stress-related mucin depletion could be a fundamental component of the pathogenesis of colitis. Experiment Overall Design: 3 individual mice from the Eeyore, Winnie or Wild-type strains were compared as groups. An Affymetrix ID was compared between groups if the ID was Present within two of the three mice within each grouping. IDs were compared by calculating the log2 of Group One average signal divided by Group 2 average signal.
2008-04-06 | E-GEOD-9913 | biostudies-arrayexpress
Project description:Transcriptional profiling of intestinal response to Citrobacter rodentium in wild-type and Nlrp12-deficient mice Four-conditions experiment, Nlrp12-deficient mouse infected by Citrobacter rodentium at day 7 versus non-infected Nlrp12-deficient mice with two biologicals replicates , Wild-type mouse infected by Citrobacter rodentium at day 7 versus non-infected Wild-type mice with two biologicals replicates and Nlrp12-deficient mouse infected by Citrobacter rodentium versus Control mouse infected by Citrobacter rodentium at 2 differents times ( day 0 and post infection at day 7 ) with three biologicals replicates
2015-07-25 | E-GEOD-59940 | biostudies-arrayexpress
Project description:Background MUC2 mucin produced by intestinal goblet cells is the major component of the intestinal mucus barrier. MUC2 homo-oligomerizes intracellularly into large secreted polymers which give mucus its viscous properties. The inflammatory bowel disease (IBD) ulcerative colitis is characterized by depleted goblet cells and a reduced mucus layer, whereas goblet cells and the mucus layer are increased in the other major inflammatory bowel disease, Crohn’s disease. Methods and Findings By murine N-ethyl-N-nitrosourea-mutagenesis we identified two distinct non-complementing missense mutations in Muc2 exons encoding N- and C-terminal homo-oligomerization domains causing an ulcerative colitis-like phenotype. Both strains developed mild spontaneous distal intestinal inflammation, chronic diarrhea, rectal bleeding and prolapse, increased susceptibility to acute and chronic colitis induced by a luminal toxin, aberrant Muc2 biosynthesis, smaller goblet cell thecae (less stored mucin) and a diminished mucus barrier. Enhanced local production of IL-1beta, TNF-alpha and IFN-gamma was seen in the distal colon. The number of leukocytes within mesenteric lymph nodes was increased five-fold and leukocytes cultured in vitro produced both Th1 and Th2 cytokines (IFN-gamma, TNF-alpha and IL-13). Intestinal permeability was increased and the luminal bacterial flora were more heavily coated with immunoglobulin as occurs in IBD. This pathology was accompanied by accumulation of the Muc2 precursor and ultrastructural and biochemical evidence of endoplasmic reticulum (ER) stress in goblet cells, activation of the unfolded protein response, and altered intestinal expression of genes involved in ER stress, inflammation, apoptosis and wound repair. Expression of mutated Muc2 oligomerization domains in vitro demonstrated that aberrant Muc2 oligomerization underlies the ER stress. These models show that mutations in Muc2 oligomerization domains can lead to aberrant assembly of the Muc2 complex leading to ER stress, a depleted mucus barrier and intestinal inflammation. In ulcerative colitis we demonstrate similar accumulation of non-glycosylated MUC2 precursor in goblet cells together with ultrastructural and biochemical evidence of ER stress even in non-inflamed intestinal tissue. Conclusions The observations that mucin misfolding and ER stress lead directly to intestinal inflammation and that ER stress and goblet cell pathology occur in ulcerative colitis suggest that ER stress-related mucin depletion could be a fundamental component of the pathogenesis of colitis. Keywords: Single gene, multiple mutant comparison
2008-03-01 | GSE9913 | GEO
Project description:Citrobacter rodentium is commonly used to elucidate mucosal responses to infection in mice developing mild disease (e.g. C57BL/6), while little is known about host responses to infection in mice developing severe disease (e.g. C3H/HeN). We report that the phyla Bacteroidetes is a minor component of the tissue-associated microbiome in uninfected C3H/HeN mice. Following infection, C. rodentium rapidly and uniformly colonises the C3H/HeN colonic mucosa, which coincides with downregulation of proteins involved in the TCA cycle and oxidative phosphorylation in intestinal epithelial cells (IECs). In contrast, we observed upregulation of DNA replication and DNA damage repair processes, as well as cholesterol biogenesis, import and export, nutritional immunity, IL-22 and INFg responses, and expression of NLRP3, in IECs. Moreover, C. rodentium triggers a staggered cell proliferation response from 3 days post infection, which correlated with a higher abundance of SLC5A9 and reduced abundance of the IEC differentiation markers SLC26A3 and CA4. Uniquely, C. rodentium triggers differential secretion of gel-forming mucins, with the number of goblet cells filled with acidic and neutral mucins dramatically increasing and decreasing, respectively. Together, these results show that despite vigorous responses, C3H/HeN mice succumb to C. rodentium infection, possibly as a result of excessive and disordered mucosal responses.
2020-01-21 | PXD012846 | Pride
Project description:We generated conditional knockout of MHCII in intestinal epithelial cells in C57BL/6 mice (I-AbΔIEC) and compared their colonic transcriptome in control and Citrobacter rodentium infected mice. I-AbWT or I-AbΔIEC mice were orally gavaged with Citrobacter rodentium DBS100
2020-02-08 | GSE144952 | GEO
Project description:The colonic inner mucus layer protects us from pathogen invasion and commensal-induced inflammation. Mucus abnormalities are common in ulcerative colitis (UC), but their cause and importance are unknown. The aim of this study was to determine the role of compositional mucus barrier alterations in UC. In this single-center case-control study, sigmoid colon biopsies were obtained from UC patients with ongoing inflammation (n=36) and in remission (n=28), and from 47 patients without inflammatory bowel disease. Mucus samples were collected from biopsies ex vivo, and their protein composition analyzed by mass spectrometry. Mucus barrier integrity and goblet cell response to microbial challenge were also assessed for a subset of patients. The core colonic mucus proteome was shown to consist of a small set of 29 secreted proteins. Patients with active UC had reduced levels of major structural components, including the mucin MUC2 (p<0.0001), also in mucus from non-inflamed segments, and their goblet cell secretory response to microbial stimulus was abrogated. Functional mucus barrier failure was observed in a subset of UC patients with and without active inflammation, and accompanied by alterations in proteins associated with mucus secretion and luminal organization. This study represents the first characterization and comparison of the mucus proteomes of the inflamed and non-inflamed colon. Core mucus structural components were reduced in active UC, also in mucus from non-inflamed segments. Thus, weakening of the mucus barrier is likely to occur early in UC pathogenesis, and represents a novel target for intervention.
2021-03-26 | PXD012632 | Pride
Project description:We report a pleiotropic disease due to loss-of-function mutations in RHBDF2, the gene encoding iRHOM2, in 2 kindreds with recurrent infections in different organs. One patient had recurrent pneumonia but no colon involvement, another had recurrent infectious hemorrhagic colitis but no lung involvement, and the other two experienced recurrent respiratory infections. Loss of iRHOM2, a rhomboid superfamily member that regulates the ADAM17 metalloproteinase, caused defective ADAM17-dependent cleavage and release of cytokines, including TNF and amphiregulin. To understand the diverse clinical phenotypes, we challenged Rhbdf2-/- mice with Pseudomonas aeruginosa by nasal gavage and observed more severe pneumonia whereas infection with Citrobacter rodentium caused worse inflammatory colitis than wild-type mice. The fecal microbiota in the colitis patient had characteristic oral species that can predispose to colitis. Thus, a new human immunodeficiency arising from iRHOM2 deficiency causes divergent disease phenotypes that can involve the local microbial environment.
2021-11-03 | GSE184876 | GEO
Project description:We report a pleiotropic disease due to loss-of-function mutations in RHBDF2, the gene encoding iRHOM2, in 2 kindreds with recurrent infections in different organs. One patient had recurrent pneumonia but no colon involvement, another had recurrent infectious hemorrhagic colitis but no lung involvement, and the other two experienced recurrent respiratory infections. Loss of iRHOM2, a rhomboid superfamily member that regulates the ADAM17 metalloproteinase, caused defective ADAM17-dependent cleavage and release of cytokines, including TNF and amphiregulin. To understand the diverse clinical phenotypes, we challenged Rhbdf2-/- mice with Pseudomonas aeruginosa by nasal gavage and observed more severe pneumonia whereas infection with Citrobacter rodentium caused worse inflammatory colitis than wild-type mice. The fecal microbiota in the colitis patient had characteristic oral species that can predispose to colitis. Thus, a new human immunodeficiency arising from iRHOM2 deficiency causes divergent disease phenotypes that can involve the local microbial environment.
2021-11-03 | GSE184875 | GEO