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Influence de la mutation NOD2 et d'un traitement antibiotique sur la colonisation et la pathogénicité d'AIEC dans l'exploration de la maladie de Crohn

Abstract : Ileal lesions of Crohn's disease (CD) patients are abnormally colonized by adherent-invasive Escherichia coli (AIEC). NOD2 gene mutations are risk factors for CD and impair bacterial clearance. Since innate immune system and commensal microbiota are critical to maintain intestinal barrier integrity, we evaluated the impact of commensal microbiota disruption induced by short term antibiotic treatment on AIEC colonization in wild type (WT) and NOD2 knock-out mice (NOD2KO), and the consequences on intestinal inflammation. Methods: After 3 days of oral antibiotic treatment, WT and NOD2KO mice were infected with 10^9 CFU AIEC once a day for 2 days. Controls are constitued by non infected mice and mice challenged with AIEC without antibiotic treatment. Animals were sacrificed 1, 5 and 60 days after AIEC administration. In parallel, mice were challenged with AIEC subsequent to a dextran sodium sulfate (DSS) treatment and sacrificed 9 days later. Ileum, colon, and mesenteric tissues were sampled for 1) AIEC quantification in ileal and colonic tissues, 2) bacterial translocation, and 3) evaluation of intestinal inflammation. Results: Without antibiotic treatment, AIEC was not able to colonize WT and NOD2KO mice. Compared with non-treated animals, antibiotic treatment led to a significant increase in ileal and colonic adherent AIEC colonization in both WT and NOD2KO mice. Persistent AIEC colonization was still observed until day 5 only in NOD2KO mice, disappearing at day 60. Mesenteric translocation of AIEC was observed only in NOD2KO mice. Morover, NOD2KO mice treated with antibiotics were more colonized by opportunistic enterobacteria. No inflammation was observed in WT and NOD2KO mice treated with antibiotics and infected with AIEC. During DSS-induced colitis, colonization and persistence of AIEC was observed in the colon. Moreover, a dramatic increase in clinical, histological, and molecular parameters of colitis was observed in mice infected with AIEC but not with a commensal E. coli strain.Conclusion: Antibiotic treatment was necessary for AIEC colonization of the gut and mesenteric tissues and persistence of AIEC was dependent on NOD2. AIEC exacerbated a preexisting DSS-induced colitis in WT mice.
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Maryline Drouet. Influence de la mutation NOD2 et d'un traitement antibiotique sur la colonisation et la pathogénicité d'AIEC dans l'exploration de la maladie de Crohn. Médecine humaine et pathologie. Université du Droit et de la Santé - Lille II, 2012. Français. ⟨NNT : 2012LIL2S004⟩. ⟨tel-00740899⟩

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