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Infect. Immun. doi:10.1128/IAI.01107-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

NF-B activation during acute Helicobacter pylori infection in mice

Unité de Pathogénie Bactérienne des Muqueuses, Unité de Recherche et d'Expertise Histotechnologie et Pathologie, Unité de Biologie Moléculaire de l'Expression Génique and Groupe d'Immunité Innée et Signalisation; Institut Pasteur, 25-28 rue du Dr Roux, Paris 75724, France

^* To whom correspondence should be addressed. Email: Richard.Ferrero{at}med.monash.edu.au. symemet{at}pasteur.fr.

	Abstract

Nuclear factor-B (NF-B) plays a key regulatory role in host cell responses to Helicobacter pylori infection in humans. Although mice are routinely used as a model to study H. pylori pathogenesis, the role of NF-B in murine cell responses to Helicobacters has not been studied in detail. We thus investigated the ability of different Helicobacter isolates to induce NF-B-dependent responses in murine gastric epithelial cells (GECs) and in transgenic mice harboring an NF-B responsive lacZ reporter gene. H. pylori and Helicobacter felis strains up-regulated the synthesis in mouse GECs of the NF-B-dependent chemokines, KC (CXCL1) and MIP-2 (CXCL2). These responses were cagPAI-independent and could be abolished by pre-treatment with a pharmacological inhibitor of NF-B. Consistent with the in vitro data, experimental Helicobacter infection of transgenic mice resulted in increased numbers of gastric epithelial cells with nuclear -galactosidase activity, indicative of specific NF-B activation. The numbers of -galactosidase-positive cells in mice were significantly increased at day 1 post-inoculation with wild-type H. pylori strains harboring or not a functional cagPAI, when compared to naive animals (p = 0.007 and p = 0.04, respectively). Strikingly, however, no differences were observed in the levels of gastric NF-B activation at day 1 post-inoculation with H. felis, nor at days 30 or 135 post-inoculation with H. pylori. This work demonstrates for the first time the induction of NF-B activation within gastric mucosal cells during acute H. pylori infection. Furthermore, the data suggest that Helicobacters may be able to regulate NF-B signaling during chronic infection.