1. A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult
- Author
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Marion Bérard, Tim Sparwasser, Rute Marques, Sophie Dulauroy, Clara Cousu, Shahed Al Bounny, Gérard Eberl, François Dejardin, Nadine Cerf-Bensussan, Ziad Al Nabhani, Microenvironnement et Immunité - Microenvironment and Immunity, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Johannes Gutenberg - Universität Mainz (JGU), Animalerie centrale (Plate-forme), Institut Pasteur [Paris], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Z.A.N. was supported by Pasteur-Roux Postdoctoral Fellowships from the Institut Pasteur. This work was supported by Institut Pasteur and INSERM, the Association François Aupetit, a Senior Research Award from the Crohn's and Colitis Foundation of America, the European Crohn’s and Colitis Organisation, the Fondation pour la Recherche Médicale, Janssen, and Innovator and Breakthrough awards from the Kenneth Rainin Foundation., We thank all the members of the Microenvironment & Immunity Unit, as well as those from the Stroma, Inflammation & Tissue Repair Unit, for support and discussion, the members of the Gnotobiology Platform of the Institut Pasteur for technical support with GF mice, the members of Biomics of the Institut Pasteur for microbial sequencing and analysis, and Ivo Gomperts Boneca (Institut Pasteur) for providing Myd88/Trif-double-deficient mice., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Institut Pasteur [Paris] (IP), and CCSD, Accord Elsevier
- Subjects
0301 basic medicine ,colitis ,[SDV]Life Sciences [q-bio] ,short-chain fatty acids ,Immunology ,Retinoic acid ,Tretinoin ,Weaning ,Biology ,T-Lymphocytes, Regulatory ,regulatory T cells ,Allergic inflammation ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Immune system ,RAR-related orphan receptor gamma ,microbiota ,medicine ,Immunology and Allergy ,Animals ,inflammatory pathology ,Colitis ,Imprinting (psychology) ,Intestinal Mucosa ,neonatal period ,Nuclear Receptor Subfamily 1, Group F, Member 3 ,medicine.disease ,Fatty Acids, Volatile ,3. Good health ,Gastrointestinal Microbiome ,[SDV] Life Sciences [q-bio] ,Mice, Inbred C57BL ,030104 developmental biology ,Infectious Diseases ,chemistry ,Animals, Newborn ,Solid food ,030220 oncology & carcinogenesis ,mucosal immunity - Abstract
International audience; Microbes colonize all body surfaces at birth and participate in the development of the immune system. In newborn mammals, the intestinal microbiota is first shaped by the dietary and immunological components of milk and then changes upon the introduction of solid food during weaning. Here, we explored the reactivity of the mouse intestinal immune system during the first weeks after birth and into adulthood. At weaning, the intestinal microbiota induced a vigorous immune response—a “weaning reaction”—that was programmed in time. Inhibition of the weaning reaction led to pathological imprinting and increased susceptibility to colitis, allergic inflammation, and cancer later in life. Prevention of this pathological imprinting was associated with the generation of RORγt+ regulatory T cells, which required bacterial and dietary metabolites—short-chain fatty acids and retinoic acid. Thus, the weaning reaction to microbiota is required for immune ontogeny, the perturbation of which leads to increased susceptibility to immunopathologies later in life.
- Published
- 2018