title: Pseudomonas fluorescens alters the intestinal barrier function by modulating IL-1β expression through hematopoietic NOD2 signaling.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: *Université Paris-Diderot, Paris, France; †INSERM UMR1149, Paris, France; ‡Labex inflamex, Sorbonne Paris-Cité, Paris, France; §INSERM UMR1163, Laboratory of Intestinal Immunity, Paris, France; ‖Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine, Paris, France; ¶LMSM EA 4312, Université de Rouen, Evreux, France; **Assistance Publique Hôpitaux de Paris, Hôpital Robert Debré, Paris, France; and ††INSERM UMR 1043, Centre de Physiopathologie de Toulouse, Université de Toulouse, Toulouse, France.
authors: Ziad
authors: Z
authors: Alnabhani
authors: Nicolas
authors: N
authors: Montcuquet
authors: Kelly
authors: K
authors: Biaggini
authors: Monique
authors: M
authors: Dussaillant
authors: Maryline
authors: M
authors: Roy
authors: Eric
authors: E
authors: Ogier-Denis
authors: Amar
authors: A
authors: Madi
authors: Abdelhak
authors: A
authors: Jallane
authors: Marc
authors: M
authors: Feuilloley
authors: Jean-Pierre
authors: JP
authors: Hugot
authors: Nathalie
authors: N
authors: Connil
authors: Fréderick
authors: F
authors: Barreau
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011551:Pseudomonas fluorescens / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017472:Receptors, Interleukin-1 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D053583:Interleukin-1beta; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1