Card9 mediates susceptibility to intestinal pathogens through microbiota modulation and control of bacterial virulence

Abstract : Objective: In association with innate and adaptive immunity, the microbiota controls the colonisation resistance against intestinal pathogens. Caspase recruitment domain 9 (CARD9), a key innate immunity gene, is required to shape a normal gut microbiota. Card9–/– mice are more susceptible to the enteric mouse pathogen Citrobacter rodentium that mimics human infections with enteropathogenic and enterohaemorrhagic Escherichia coli. Here, we examined how CARD9 controls C. rodentium infection susceptibility through microbiota-dependent and microbiota-independent mechanisms. Design: C. rodentium infection was assessed in conventional and germ-free (GF) wild-type (WT) and Card9–/– mice. To explore the impact of Card9–/–microbiota in infection susceptibility, GF WT mice were colonised with WT (WT→GF) or Card9–/– (Card9–/–→GF) microbiota before C. rodentium infection. Microbiota composition was determined by 16S rDNA gene sequencing. Inflammation severity was determined by histology score and lipocalin level. Microbiota–host immune system interactions were assessed by quantitative PCR analysis. Results: CARD9 controls pathogen virulence in a microbiota-independent manner by supporting a specific humoral response. Higher susceptibility to C. rodentium-induced colitis was observed in Card9–/–→GF mice. The microbiota of Card9–/– mice failed to outcompete the monosaccharide-consuming C. rodentium, worsening the infection severity. A polysaccharide-enriched diet counteracted the ecological advantage of C. rodentium and the defective pathogen-specific antibody response in Card9–/– mice. Conclusions: CARD9 modulates the susceptibility to intestinal infection by controlling the pathogen virulence in a microbiota-dependent and microbiota-independent manner. Genetic susceptibility to intestinal pathogens can be overridden by diet intervention that restores humoural immunity and a competing microbiota.
Liste complète des métadonnées


http://hal.upmc.fr/hal-01586076
Contributeur : Gestionnaire Hal-Upmc <>
Soumis le : mardi 12 septembre 2017 - 14:20:58
Dernière modification le : jeudi 14 septembre 2017 - 01:08:31

Fichier

 Accès restreint
Fichier visible le : 2018-02-08

Connectez-vous pour demander l'accès au fichier

Identifiants

Citation

Bruno Lamas, Marie-Laure Michel, Nadine Waldschmitt, Hang-Phuong Pham, Vassiliki Zacharioudaki, et al.. Card9 mediates susceptibility to intestinal pathogens through microbiota modulation and control of bacterial virulence. Gut, BMJ Publishing Group, 2017, pp.314195. <10.1136/gutjnl-2017-314195>. <hal-01586076>

Partager

Métriques

Consultations de la notice

24