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Article Dans Une Revue Infection and Immunity Année : 2015

Oral tolerance failure upon neonatal gut colonization with Escherichia coli producing the genotoxin colibactin

Marion Gillet
  • Fonction : Auteur
Sandrine Ménard

Résumé

The intestinal barrier controls the balance between tolerance and immunity to luminal antigens. When this finely tuned equilibrium is deregulated, inflammatory disorders can occur. There is a concomitant increase, in urban populations of developed countries, of immune-mediated diseases along with a shift in Escherichia coli population from the declining phylogenetic group A to the newly dominant group B2, including commensal strains producing a genotoxin called colibactin that massively colonized the gut of neonates. Here, we showed that mother-to-offspring early gut colonization by colibactin-producing E. coli impairs intestinal permeability and enhances the transepithelial passage of luminal antigen, leading to an increased immune activation. Functionally, this was accompanied by a dramatic increase in local and systemic immune responses against a fed antigen, decreased regulatory T cell population, tolerogenic dendritic cells, and enhanced mucosal delayed-type hypersensitivity response. Conversely, the abolition of colibactin expression by mutagenesis abrogates the alteration of oral tolerance induced by neonatal colonization by E. coli. In conclusion, the vertical colonization by E. coli producing the genotoxin colibactin enhances intestinal translocation and subsequently alters oral tolerance. Thus, early colonization by E. coli from the newly dominant phylogenetic group B2, which produces colibactin, may represent a risk factor for the development of immune-mediated diseases.

Dates et versions

hal-02634629 , version 1 (27-05-2020)

Identifiants

Citer

Thomas Secher, Delphine Payros, Camille Brehin, Michèle Boury, Claude Watrin, et al.. Oral tolerance failure upon neonatal gut colonization with Escherichia coli producing the genotoxin colibactin. Infection and Immunity, 2015, 83 (6), pp.2420-2429. ⟨10.1128/IAI.00064-15⟩. ⟨hal-02634629⟩
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