Gnotobiotic IL-10−/−; NF-κBEGFP Mice Develop Rapid and Severe Colitis Following Campylobacter jejuni Infection

Lippert, Elisabeth; Karrasch, Thomas; Sun, Xiaolun; Allard, Brigitte; Herfarth, Hans H; Threadgill, Deborah S.; Jobin, Christian

doi:10.1371/journal.pone.0007413

Cited by 45 publications

(56 citation statements)

References 35 publications

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“…Colonoscopy was performed using a ‘Coloview System' (Karl Storz Veterinary Endoscopy) as described previously68. The mice were anaesthetized using 1.5 to 2% isoflurane and ∼4 cm of the colon from the anal verge from the splenic flexure was visualized.…”

Section: Methodsmentioning

confidence: 99%

Altered intestinal microbiota–host mitochondria crosstalk in new onset Crohn’s disease

et al. 2016

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Intestinal microbial dysbiosis is associated with Crohn's disease (CD). However, the mechanisms leading to the chronic mucosal inflammation that characterizes this disease remain unclear. In this report, we use systems-level approaches to study the interactions between the gut microbiota and host in new-onset paediatric patients to evaluate causality and mechanisms of disease. We report an altered host proteome in CD patients indicative of impaired mitochondrial functions. In particular, mitochondrial proteins implicated in H2S detoxification are downregulated, while the relative abundance of H2S microbial producers is increased. Network correlation analysis reveals that Atopobium parvulum controls the central hub of H2S producers. A. parvulum induces pancolitis in colitis-susceptible interleukin-10-deficient mice and this phenotype requires the presence of the intestinal microbiota. Administrating the H2S scavenger bismuth mitigates A. parvulum-induced colitis in vivo. This study reveals that host–microbiota interactions are disturbed in CD and thus provides mechanistic insights into CD pathogenesis.

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Section: Methodsmentioning

confidence: 99%

Altered intestinal microbiota–host mitochondria crosstalk in new onset Crohn’s disease

et al. 2016

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“…11 Primary antibodies used were phospho-p70S6K (T389) and p70S6K (Cell Signaling), EGFP (Sigma), LC3 I/II (MBL) and Actin (BP Biomedicals).…”

Section: Methodsmentioning

confidence: 99%

“…We recently established an acute model of campylobacteriosis using germ-free Il10 −/− mice. 11 In this model, C. jejuni induces a rapid (5 days) and robust inflammatory (bloody diarrhea) response to the microorganism. However, the cellular and molecular details responsible for this host response remained undefined.…”

Section: Introductionmentioning

confidence: 99%

Campylobacter jejuni Induces Colitis Through Activation of Mammalian Target of Rapamycin Signaling

2012

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BACKGROUND & AIMS Campylobacter jejuni is the worldwide leading cause of bacterial-induced enteritis. The molecular and cellular events that lead to campylobacteriosis are poorly understood. We identify mammalian target of rapamycin (mTOR) as a signaling pathway that leads to C jejuni-induced intestinal inflammation. METHODS Germ-free (control) or conventionally-derived interleukin (Il)10−/− mice that express enhanced green fluorescent protein under the control of NF-κB (Il10 −/−; NF-κBEGFP mice) were infected with C jejuni (109 CFU/mouse) for 12 days; their responses were determined using histologic, semi-quantitative reverse transcription PCR, fluorescence in situ hybridization, transmission electron microscopy, and tissue culture analyses. mTOR signaling was blocked by daily intraperitoneal injections of the pharmacologic inhibitor rapamycin (1.5 mg/kg). CD4+ T cells were depleted by intraperitoneal injections of antibodies against CD4 (0.5 mg/mouse, every 3 days). Bacterial survival in splenocytes was measured using a gentamycin killing assay. RESULTS C jejuni induced intestinal inflammation, which correlated with activation of mTOR signaling and neutrophil infiltration. The inflamed intestines of these mice had increased levels of Il-1β, Cxcl2, Il-17a, and EGFP; C jejuni localized to colons and extra-intestinal tissues of infected Il10−/−; NF-κBEGFP mice, compared with controls. Rapamycin, administered before or after introduction of C jejuni, blocked C jejuni-induced intestinal inflammation and bacterial accumulation. LC3II processing and killing of C jejuni were increased in splenocytes incubated with rapamycin, compared with controls. CONCLUSIONS mTOR signaling mediates C jejuni-induced colitis in Il10−/− mice, independently of T-cell activation. Factors involved in mTOR signaling might be therapeutic targets for campylobacteriosis.

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“…In agreement, although C . jejuni products elicit an inflammatory response from intestinal epithelial cells through the activation of NF-κB and the release of CXCL8 [132,133], Nod2 KO mice failed to develop colitis [134,135]. However, NOD2 signaling seems critical to control campylobacteriosis in IL- 10 KO mice by improving nitric-oxide-dependent bactericidal activity [135].…”

Section: Bacteriamentioning

confidence: 99%

Nod2: The intestinal gate keeper

et al. 2017

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Nucleotide-binding oligomerization domain 2 (NOD2) is an intracellular pattern recognition receptor that senses bacterial peptidoglycan (PGN)-conserved motifs in cytosol and stimulates host immune response. The association of NOD2 mutations with a number of inflammatory pathologies, including Crohn disease (CD), Graft-versus-host disease (GVHD), and Blau syndrome, highlights its pivotal role in host–pathogen interactions and inflammatory response. Stimulation of NOD2 by its ligand (muramyl dipeptide) activates pro-inflammatory pathways such as nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs), and Caspase-1. A loss of NOD2 function may result in a failure in the control of microbial infection, thereby initiating systemic responses and aberrant inflammation. Because the ligand of Nod2 is conserved in both gram-positive and gram-negative bacteria, NOD2 detects a wide variety of microorganisms. Furthermore, current literature evidences that NOD2 is also able to control viruses’ and parasites’ infections. In this review, we present and discuss recent developments about the role of NOD2 in shaping the gut commensal microbiota and pathogens, including bacteria, viruses, and parasites, and the mechanisms by which Nod2 mutations participate in disease occurrence.

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Gnotobiotic IL-10−/−; NF-κBEGFP Mice Develop Rapid and Severe Colitis Following Campylobacter jejuni Infection

Cited by 45 publications

References 35 publications

Altered intestinal microbiota–host mitochondria crosstalk in new onset Crohn’s disease

Altered intestinal microbiota–host mitochondria crosstalk in new onset Crohn’s disease

Campylobacter jejuni Induces Colitis Through Activation of Mammalian Target of Rapamycin Signaling

Nod2: The intestinal gate keeper

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