Pseudomonas fluorescens alters the intestinal barrier function by modulating IL-1β expression through hematopoietic NOD2 signaling

Ileal Crohn's disease is related to NOD2 mutations and to a gut barrier dysfunction. Pseudomonas fluorescens has also been associated with ileal Crohn's disease. The aim of this study was to determine the impact of P. fluorescens on the paracellular permeability in ileum and Peyer's p...

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Veröffentlicht in:Inflammatory bowel diseases 2015-03, Vol.21 (3), p.543-555
Hauptverfasser: Alnabhani, Ziad, Montcuquet, Nicolas, Biaggini, Kelly, Dussaillant, Monique, Roy, Maryline, Ogier-Denis, Eric, Madi, Amar, Jallane, Abdelhak, Feuilloley, Marc, Hugot, Jean-Pierre, Connil, Nathalie, Barreau, Fréderick
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container_end_page 555
container_issue 3
container_start_page 543
container_title Inflammatory bowel diseases
container_volume 21
creator Alnabhani, Ziad
Montcuquet, Nicolas
Biaggini, Kelly
Dussaillant, Monique
Roy, Maryline
Ogier-Denis, Eric
Madi, Amar
Jallane, Abdelhak
Feuilloley, Marc
Hugot, Jean-Pierre
Connil, Nathalie
Barreau, Fréderick
description Ileal Crohn's disease is related to NOD2 mutations and to a gut barrier dysfunction. Pseudomonas fluorescens has also been associated with ileal Crohn's disease. The aim of this study was to determine the impact of P. fluorescens on the paracellular permeability in ileum and Peyer's patches. To explore this question, in vivo and ex vivo experiments were performed in wild-type, Nod2, Nod2, and IL-1R mice together with in vitro analyses using the Caco-2 (epithelial) and the THP-1 (monocyte) human cell lines. Pseudomonas fluorescens increased the paracellular permeability of the intestinal mucosa through the secretion of IL-1β by the immune cell populations and the activation of myosin light chain kinase in the epithelial cells. Induction of the IL-1β pathway required the expression of Nod2 in the hematopoietic compartment, and muramyl dipeptide (a Nod2 ligand) had an inhibitory effect. Pseudomonas fluorescens thus alters the homeostasis of the epithelial barrier function by a mechanism similar to that previously observed for Yersinia pseudotuberculosis. This work further documents a putative role of psychrotrophic bacteria in Crohn's disease.
doi_str_mv 10.1097/MIB.0000000000000291
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Pseudomonas fluorescens has also been associated with ileal Crohn's disease. The aim of this study was to determine the impact of P. fluorescens on the paracellular permeability in ileum and Peyer's patches. To explore this question, in vivo and ex vivo experiments were performed in wild-type, Nod2, Nod2, and IL-1R mice together with in vitro analyses using the Caco-2 (epithelial) and the THP-1 (monocyte) human cell lines. Pseudomonas fluorescens increased the paracellular permeability of the intestinal mucosa through the secretion of IL-1β by the immune cell populations and the activation of myosin light chain kinase in the epithelial cells. Induction of the IL-1β pathway required the expression of Nod2 in the hematopoietic compartment, and muramyl dipeptide (a Nod2 ligand) had an inhibitory effect. Pseudomonas fluorescens thus alters the homeostasis of the epithelial barrier function by a mechanism similar to that previously observed for Yersinia pseudotuberculosis. 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subjects Animals
Bacteriology
Biochemistry, Molecular Biology
Blotting, Western
Caco-2 Cells
Cell Behavior
Cell Membrane Permeability
Cells, Cultured
Cellular Biology
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - metabolism
Hematopoietic Stem Cells - microbiology
Humans
Interleukin-1beta - genetics
Interleukin-1beta - metabolism
Intestinal Mucosa - cytology
Intestinal Mucosa - metabolism
Intestinal Mucosa - microbiology
Life Sciences
Macrophages - cytology
Macrophages - metabolism
Macrophages - microbiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Microbiology and Parasitology
Molecular biology
Nod2 Signaling Adaptor Protein - genetics
Nod2 Signaling Adaptor Protein - metabolism
Nod2 Signaling Adaptor Protein - physiology
Pseudomonas fluorescens - physiology
Real-Time Polymerase Chain Reaction
Receptors, Interleukin-1 - physiology
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Signal Transduction
title Pseudomonas fluorescens alters the intestinal barrier function by modulating IL-1β expression through hematopoietic NOD2 signaling
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