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Anti-Inflammatory Effect of Lactobacillus casei on Shigella-Infected Human Intestinal Epithelial Cells

Meng-Tsung Tien, Stephen E. Girardin, Béatrice Regnault, Lionel Le Bourhis, Marie-Agnès Dillies, Jean-Yves Coppée, Raphaëlle Bourdet-Sicard, Philippe J. Sansonetti and Thierry Pédron
J Immunol January 15, 2006, 176 (2) 1228-1237; DOI: https://doi.org/10.4049/jimmunol.176.2.1228
Meng-Tsung Tien
*Pathogénie Microbienne Moléculaire Unit, Institut National de la Santé et de la Recherche Médicale U389,
†DNA Chip Platform, Genopole, and
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Stephen E. Girardin
*Pathogénie Microbienne Moléculaire Unit, Institut National de la Santé et de la Recherche Médicale U389,
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Béatrice Regnault
†DNA Chip Platform, Genopole, and
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Lionel Le Bourhis
‡Imunité Innée et Signalisation, Pasteur Institute, Paris, France; and
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Marie-Agnès Dillies
†DNA Chip Platform, Genopole, and
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Jean-Yves Coppée
†DNA Chip Platform, Genopole, and
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Raphaëlle Bourdet-Sicard
§Danone Vitapole, Nutrivaleur, Palaiseau, France
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Philippe J. Sansonetti
*Pathogénie Microbienne Moléculaire Unit, Institut National de la Santé et de la Recherche Médicale U389,
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Thierry Pédron
*Pathogénie Microbienne Moléculaire Unit, Institut National de la Santé et de la Recherche Médicale U389,
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This article has a correction. Please see:

  • Errata - March 15, 2006

Abstract

Shigella invades the human intestinal mucosa, thus causing bacillary dysentery, an acute recto-colitis responsible for lethal complications, mostly in infants and toddlers. Conversely, commensal bacteria live in a mutualistic relationship with the intestinal mucosa that is characterized by homeostatic control of innate responses, thereby contributing to tolerance to the flora. Cross-talk established between commensals and the intestinal epithelium mediate this active process, the mechanisms of which remain largely uncharacterized. Probiotics such as Lactobacillus casei belong to a subclass of these commensals that modulate mucosal innate responses and possibly display anti-inflammatory properties. We analyzed whether L. casei could attenuate the pro-inflammatory signaling induced by Shigella flexneri after invasion of the epithelial lining. Cultured epithelial cells were infected with L. casei, followed by a challenge with S. flexneri. Using macroarray DNA chips, we observed that L. casei down-regulated the transcription of a number of genes encoding pro-inflammatory effectors such as cytokines and chemokines and adherence molecules induced by invasive S. flexneri. This resulted in an anti-inflammatory effect that appeared mediated by the inhibition of the NF-κB pathway, particularly through stabilization of I-κBα. In a time-course experiment using GeneChip hybridization analysis, the expression of many genes involved in ubiquitination and proteasome processes were modulated during L. casei treatment. Thus, L. casei has developed a sophisticated means to maintain intestinal homeostasis through a process that involves manipulation of the ubiquitin/proteasome pathway upstream of I-κBα.

  • Received March 25, 2005.
  • Accepted October 25, 2005.
  • Copyright © 2006 by The American Association of Immunologists
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The Journal of Immunology: 176 (2)
The Journal of Immunology
Vol. 176, Issue 2
15 Jan 2006
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Anti-Inflammatory Effect of Lactobacillus casei on Shigella-Infected Human Intestinal Epithelial Cells
Meng-Tsung Tien, Stephen E. Girardin, Béatrice Regnault, Lionel Le Bourhis, Marie-Agnès Dillies, Jean-Yves Coppée, Raphaëlle Bourdet-Sicard, Philippe J. Sansonetti, Thierry Pédron
The Journal of Immunology January 15, 2006, 176 (2) 1228-1237; DOI: 10.4049/jimmunol.176.2.1228

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Anti-Inflammatory Effect of Lactobacillus casei on Shigella-Infected Human Intestinal Epithelial Cells
Meng-Tsung Tien, Stephen E. Girardin, Béatrice Regnault, Lionel Le Bourhis, Marie-Agnès Dillies, Jean-Yves Coppée, Raphaëlle Bourdet-Sicard, Philippe J. Sansonetti, Thierry Pédron
The Journal of Immunology January 15, 2006, 176 (2) 1228-1237; DOI: 10.4049/jimmunol.176.2.1228
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