1. Oral Tolerance Failure upon Neonatal Gut Colonization with Escherichia coli Producing the Genotoxin Colibactin
- Author
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Claude Watrin, Maïwenn Olier, Thomas Secher, Abdelhadi Saoudi, Marion Gillet, Sandrine Ménard, Vassilia Theodorou, Eric Oswald, Delphine Payros, Isabelle Bernard-Cadenat, Michèle Boury, Camille Brehin, ProdInra, Migration, Centre de Physiopathologie de Toulouse-Purpan (INSERM U563 - CNRS UMR1037), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut Claudius Regaud-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de lutte contre le cancer (CLCC)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Recherche Agronomique (INRA), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Service Bactériologie et hygiène [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Agence Nationale de la Recherche ANR-13-BSV1-0028-01 ANR-09-MIE-005, French government through the Investments for the Future program ANR-11-EQPX-0003, Conseil Regional de Midi-Pyrenees 12050986, platform Aninfimip, Centre National de la Recherche Scientifique (CNRS)-Centre de lutte contre le cancer (CLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut Claudius Regaud, Hôpital Purpan, Service de Bactériologie-Hygiène, and Centre Hospitalier Universitaire de Toulouse
- Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology ,Regulatory T cell ,Immunology ,Population ,Biology ,medicine.disease_cause ,Microbiology ,03 medical and health sciences ,Immune system ,Antigen ,Pregnancy ,Immunity ,Escherichia coli ,medicine ,Animals ,Colonization ,Rats, Wistar ,education ,[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology ,030304 developmental biology ,2. Zero hunger ,Host Response and Inflammation ,0303 health sciences ,education.field_of_study ,Intestinal permeability ,030306 microbiology ,oral tolerance ,neonatal colonization ,medicine.disease ,Rats ,3. Good health ,Gastrointestinal Tract ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Infectious Diseases ,medicine.anatomical_structure ,Animals, Newborn ,Polyketides ,Carrier State ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,Parasitology ,colibactin ,Peptides - Abstract
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.
- Published
- 2015