Titre :

NADPH oxidase deficient mice develop colitis and bacteremia upon infection with normally avirulent, TTSS-1- and TTSS-2-deficient Salmonella Typhimurium.

Auteur(s) :

Felmy, Boas [Auteur]
Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] [ETH Zürich]
Songhet, Pascal [Auteur]
Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] [ETH Zürich]
Slack, Emma Marie Caroline [Auteur]
Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] [ETH Zürich]
Müller, Andreas [Auteur]
Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] [ETH Zürich]
Kremer, Marcus [Auteur]
Van Maele, Laurye [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Cayet, delphine [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Heikenwalder, Mathias [Auteur]
Sirard, Jean-Claude [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Hardt, Wolf-Dietrich [Auteur correspondant]
Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] [ETH Zürich]

Titre de la revue :

PLoS ONE

Pagination :

e77204

Éditeur :

Public Library of Science

Date de publication :

2013

ISSN :

1932-6203

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Immunologie

Résumé en anglais : [en]

Infections, microbe sampling and occasional leakage of commensal microbiota and their products across the intestinal epithelial cell layer represent a permanent challenge to the intestinal immune system. The production of ...
Lire la suite >Infections, microbe sampling and occasional leakage of commensal microbiota and their products across the intestinal epithelial cell layer represent a permanent challenge to the intestinal immune system. The production of reactive oxygen species by NADPH oxidase is thought to be a key element of defense. Patients suffering from chronic granulomatous disease are deficient in one of the subunits of NADPH oxidase. They display a high incidence of Crohn's disease-like intestinal inflammation and are hyper-susceptible to infection with fungi and bacteria, including a 10-fold increased risk of Salmonellosis. It is not completely understood which steps of the infection process are affected by the NADPH oxidase deficiency. We employed a mouse model for Salmonella diarrhea to study how NADPH oxidase deficiency (Cybb (-/-)) affects microbe handling by the large intestinal mucosa. In this animal model, wild type S. Typhimurium causes pronounced enteropathy in wild type mice. In contrast, an avirulent S. Typhimurium mutant (S.Tm(avir); invGsseD), which lacks virulence factors boosting trans-epithelial penetration and growth in the lamina propria, cannot cause enteropathy in wild type mice. We found that Cybb (-/-) mice are efficiently infected by S.Tm(avir) and develop enteropathy by day 4 post infection. Cell depletion experiments and infections in Cybb (-/-) Myd88 (-/-) mice indicated that the S.Tm(avir)-inflicted disease in Cybb (-/-) mice hinges on CD11c(+)CX3CR1(+) monocytic phagocytes mediating colonization of the cecal lamina propria and on Myd88-dependent proinflammatory immune responses. Interestingly, in mixed bone marrow chimeras a partial reconstitution of Cybb-proficiency in the bone marrow derived compartment was sufficient to ameliorate disease severity. Our data indicate that NADPH oxidase expression is of key importance for restricting the growth of S.Tm(avir) in the mucosal lamina propria. This provides important insights into microbe handling by the large intestinal mucosa and the role of NADPH oxidase in maintaining microbe-host mutualism at this exposed body surface.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL