NOD2 transmissible microbiota predispose WT mice to inflammation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE36481 | GEO | 2013/01/02
SECONDARY ACCESSION(S): PRJNA153517
REPOSITORIES: GEO
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Project description:Instability in the composition of gut bacterial communities, referred as dysbiosis, has been associated with important human intestinal disorders such as Crohn’s disease and colorectal cancer. Our data showed that Nod2-mediated risk of intestinal inflammation in colitis model is communicable to WT mice by cohousing. Here, we investigated if Nod2-deficient mice microbiota is able to change transcript profiles in Nod2-immunocompetent mice (C57Bl6/J mice) independently of colitis. Analysis used RNA extracted from colonic mucosa of C57Bl/6J mice co-housed with Nod2-deficient mice and C57Bl/6J mice alone. Direct comparisons of 4 biologicals replicates of C57Bl/6J mice cohoused with Nod2-deficient mice vs C57Bl/6J mice were performed.
2013-01-02 | E-GEOD-36481 | biostudies-arrayexpress
Project description:Instability in the composition of gut bacterial communities, referred as dysbiosis, has been associated with important human intestinal disorders such as Crohn’s disease and colorectal cancer. Here, we show that dysbiosis coupled to Nod2 or Rip2 deficiency suffices to cause an increased risk for intestinal inflammation and colitis-associated carcinogenesis in mice. Aggravated epithelial lesions and dysplasia upon chemical-induced injury associated with loss of Nod2 or Rip2 can be prevented by antibiotics or anti-IL6R treatment. Nod2-mediated risk for intestinal inflammation and colitis-associated tumorigenesis is communicable through maternally-transmitted microbiota even to wild-type hosts. Disease progression was identified to drive complex NOD2-dependent changes of the colonic-associated microbiota. Reciprocal microbiota transplantation rescues the vulnerability of Nod2-deficient mice to colonic injury. Altogether, our results unveil an unexpected function for NOD2 in shaping a protective assembly of gut microbial communities, providing a rationale for intentional manipulation of genotype-dependent dysbiosis as a causative therapeutic principle in chronic intestinal inflammation.
2013-01-02 | GSE32421 | GEO
Project description:Instability in the composition of gut bacterial communities, referred as dysbiosis, has been associated with important human intestinal disorders such as CrohnM-bM-^@M-^Ys disease and colorectal cancer. Here, we show that dysbiosis coupled to Nod2 or Rip2 deficiency suffices to cause an increased risk for intestinal inflammation and colitis-associated carcinogenesis in mice. Aggravated epithelial lesions and dysplasia upon chemical-induced injury associated with loss of Nod2 or Rip2 can be prevented by antibiotics or anti-IL6R treatment. Nod2-mediated risk for intestinal inflammation and colitis-associated tumorigenesis is communicable through maternally-transmitted microbiota even to wild-type hosts. Disease progression was identified to drive complex NOD2-dependent changes of the colonic-associated microbiota. Reciprocal microbiota transplantation rescues the vulnerability of Nod2-deficient mice to colonic injury. Altogether, our results unveil an unexpected function for NOD2 in shaping a protective assembly of gut microbial communities, providing a rationale for intentional manipulation of genotype-dependent dysbiosis as a causative therapeutic principle in chronic intestinal inflammation. Analysis used RNA extracted from colonic mucosa of untreated, antibiotics-treated or metronidazole-treated C57Bl/6J and Nod2-deficient mice in CAC model. Direct comparisons were performed as follow: C57Bl/6J untreated mice vs Nod2-deficient untreated mice, C57Bl/6J antibiotics-treated mice vs Nod2-deficient antibiotics-treated mice, C57Bl/6J metronidazole-treated mice vs Nod2-deficient metronidazole-treated mice, C57Bl/6J untreated mice vs C57Bl/6J antibiotics-treated mice, C57Bl/6J untreated mice vs C57Bl/6J metronidazole-treated mice, Nod2-deficient untreated mice vs Nod2-deficient antibiotics-treated mice, Nod2-deficient untreated mice vs Nod2-deficient metronidazole-treated mice. Indirect comparisons with control data were made across multiple arrays with raw data pulled from different channels for data analysis.
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Project description:Nod2 has been extensively characterized as a bacterial sensor that induces an antimicrobial and inflammatory gene expression program. Therefore, it is unclear why Nod2 mutations that disrupt bacterial recognition are paradoxically among the highest risk factors for Crohn’s disease, which involves an exaggerated immune response directed at intestinal bacteria. Previous studies from our lab have shown that mice deficient in Atg16L1, another Crohns disease susceptibility gene, develop abnormalities in Paneth cells, specialized epithelial cells in the small intestine involved in antimicrobial responses. The goal of our study is to determine whether Nod2 deficiency leads to differences in the transcriptional profile of Paneth cells, ultimately leading to small intestinal inflammation. Small intestinal sections (ileum) of 8 week old WT and Nod2-/- mice were fixed in methacarn and embedded in paraffin. The Leica LMD6000 Laser Microdissection system was used to capture crypt base epithelial cells to enrich for Paneth cells. RNA was extracted from these cells, followed by cDNA synthesis and qPCR to confirm enrichment of Paneth cells using unique markers (a-defensins).
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Project description:Nod2 has been extensively characterized as a bacterial sensor that induces an antimicrobial and inflammatory gene expression program. Therefore, it is unclear why Nod2 mutations that disrupt bacterial recognition are paradoxically among the highest risk factors for Crohn’s disease, which involves an exaggerated immune response directed at intestinal bacteria. Previous studies from our lab have shown that mice deficient in Atg16L1, another Crohns disease susceptibility gene, develop abnormalities in Paneth cells, specialized epithelial cells in the small intestine involved in antimicrobial responses. The goal of our study is to determine whether Nod2 deficiency leads to differences in the transcriptional profile of Paneth cells, ultimately leading to small intestinal inflammation.
2014-07-01 | GSE58948 | GEO
Project description:Crohn’s disease (CD) is a chronic inflammatory intestinal disease, often characterized by aberrant healing and stricturing complications. Mechanisms underlying NOD2-pathogenicity and salvage pathways in anti-TNF and refractory patients remain largely uncharacterized. Here we show that loss of NOD2 function leads to aberrant activated fibroblast and macrophage homeostasis through the upregulation of a pathogenic signature, and propose new precision therapeutic approaches involving gp130 blockade for select CD patients, to potentially supplement anti-TNF therapy
2021-03-05 | GSE150498 | GEO
Project description:We previously found that mice deficient in the CD susceptibility gene Nod2 develop small intestinal abnormalities including impaired mucus production by goblet cells and susceptibility to injury, which were associated with interferon-gamma producing intraepithelial lymphocytes. These abnormalities were caused by a striking expansion of a common member of the microbiota, Bacteroides vulgatus. Remarkably, infection of Nod2-deficient mice with the helminth Trichuris muris led to a TH2 response that eliminated B. vulgatus colonization and intestinal abnormalities. In addition, treatment with recombinant IL13 (rIL13) or recombinant IL4 reduced B. vulgatus levels and eliminated goblet cell defects, suggesting that type 2 cytokines alone can reverse intestinal abnormalities in the absence of helminth infection. To determine the mechanism by which type 2 cytokines protected Nod2-/- mice from intestinal abnormalities, we performed RNA-seq on small intestinal tissue from WT, Nod2-/- and rIL13 treated Nod2-/- mice. We found that rIL13 treatment induced a wound healing response characterized by M2 macrophage activation genes. Hence, type 2 cytokines can reverse inflammatory imbalances in the composition of the gut microbiota that occurs in a genetically susceptible host.
2016-04-28 | GSE76504 | GEO
Project description:The goal of this project is to find out whether human intestinal IgA1 and IgA2 secretion, transport and reactivity towards the microbiota might be involved in dysbiosis induction during Crohn’s disease and Ulcerative colitis. Mass spectrometry was used to characterize SIgA from Crohn’s disease patient and Ulcerative colitis patient, in term of O- and N-glycosylation in order to study their reverse transcytosis capacity and their role in intestinal inflammation.
2022-06-27 | PXD024060 | Pride
Project description:Recognition and response to gram-positive bacteria by macrophages and dendritic cells is mediated in part through TLR2. We found that that Streptococcus pneumoniae cell wall fragments, containing primarily peptidoglycan and teichoic acids, induced prodigious secretion of IL-10 from macrophages and dendritic cells and was dependent on TLR2 and NOD2, a cytoplasmic CARD-NACHT-LRR protein encoded by Card15. IL-10 secretion in response to cell walls was also dependent on RICK/RIP2, a kinase associated with NOD2, and MYD88 but independent of the ERK/p38 pathway. The reduction of IL-10 secretion by cell wall-activated NOD2-deficient myeloid–derived cells translated into downstream effects on IL-10 target gene expression and elevations in subsets of pro-inflammatory cytokine expression normally restrained by autocrine/paracrine effects of IL-10. Since NOD2 is linked to aberrant immune responses in Crohn’s Disease patients bearing mutations in CARD15, the temporal and quantitative effects of the TLR2/NOD/RICK pathway on IL-10 secretion may affect homeostatic control of immune responses to gram-positive bacteria. Keywords: immune response simulated pathogen response
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| PRJEB21817 | ENA