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* Unité de Pathogénie Microbienne Moléculaire, Département de Biologie Cellulaire et Infection,
Unité Institut National de la Santé et de la Recherche Médicale U786, and
Plateforme Puces à ADN, Institut Pasteur, Paris; and
Unité Institut National de la Santé et de la Recherche Médicale U661, Département d’Oncologie Cellulaire et Moléculaire, Institut de Génomique Fonctionnelle, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5203, Université de Montpellier I et Université de Montpellier II, Montpellier, France
The intestinal tract of adult mice is naturally resistant to infection by Shigella, the causative agent of bacillary dysentery in humans. Conversely, newborn mice are highly susceptible to intragastric Shigella infection and develop inflammatory lesions of the jejunal mucosa, very similar to those observed in the colon of dysenteric patients. However, the susceptibility period is short and one week after birth, animals have acquired a status of resistance characteristic of adult animals. To identify the developmental changes controlling the switch from disease susceptibility to resistance, we performed global gene expression analysis on noninfected and infected intestinal tissues taken from 4-day- and 7-day-old animals. Transcriptomic analysis of 4-day-old mice infected with the invasive Shigella strain showed a profile reflecting a strong inflammatory response with no evidence for retro-control, suggesting that the invasive process had occurred, whereas inflammation had been controlled after infection with the noninvasive strain. Differences in gene expression profiles between noninfected 4-day- and 7-day-old mice corresponded mainly to genes encoding anti-microbial peptides and proteases, suggesting that these molecules could be candidates for host antimicrobial resistance in the course of shigellosis. Indeed, expression of genes specific of Paneth cells was higher in 7-day- than in 4-day-old mice, and histological analysis indicated that Paneth cells were present only at day 7. Finally, using Sox9flox/flox-vil-cre mice, we showed that depletion of Paneth cells restored the susceptibility to Shigella of 7-day-old mice, clearly indicating that Paneth cells development is crucial for the clearance of intestinal infection.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from Transversal Research Program from Institut Pasteur (PTR 187), from Institut National de la Santé et de la Recherche Médicale, and from the Genopole of Institut Pasteur. The Affymetrix station of the Pasteur Institute was purchased with a donation from Dr. R. Nunnikhoven. P.J.S. is a Howard Hughes Medical Institute scholar.
2 M.-I.F. and B.R. contributed equally to this work.
3 Present address: Unité Institut National de la Santé et de la Recherche Médicale U653, Immunité et Cancer, Institut Curie, 26 rue d’Ulm, 75005 Paris, France.
4 Address correspondence and reprint requests to Dr. Philippe J. Sansonetti, Unité de Pathogénie Microbienne Moléculaire, Institut National de la Santé et de la Recherche Médicale U786, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris, cedex 15, France. E-mail address: psanson{at}pasteur.fr
5 Abbreviations used in this paper: PMN, polymorphonuclear leukocyte; DiBAC4, bis-(1,3-dibutylbarbituric acid)-trimethine oxanol; CD, Crohn’s disease.
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  J. R. Mastroianni and A. J. Ouellette {alpha}-Defensins in Enteric Innate Immunity: FUNCTIONAL PANETH CELL {alpha}-DEFENSINS IN MOUSE COLONIC LUMEN J. Biol. Chem., October 9, 2009; 284(41): 27848 - 27856. [Abstract] [Full Text] [PDF]
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