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Immunity. 2019 May 21;50(5):1276-1288.e5. doi: 10.1016/j.immuni.2019.02.014. Epub 2019 Mar 19.

A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult.

Author information

1
Microenvironment & Immunity Unit, Institut Pasteur, 75724 Paris, France; INSERM U1224, 75724 Paris, France.
2
Department of Medical Microbiology and Hygiene, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany.
3
Institut Pasteur, DTPS, Animalerie Centrale, Centre de Gnotobiologie, 75724 Paris, France.
4
Institute Imagine, U1163, INSERM, 75015 Paris, France; Université Paris Descartes-Sorbonne Paris Cité, 75006 Paris, France.
5
Microenvironment & Immunity Unit, Institut Pasteur, 75724 Paris, France; INSERM U1224, 75724 Paris, France. Electronic address: gerard.eberl@pasteur.fr.

Abstract

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.

KEYWORDS:

colitis; inflammatory pathology; microbiota; mucosal immunity; neonatal period; regulatory T cells; short-chain fatty acids; weaning

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PMID:
30902637
DOI:
10.1016/j.immuni.2019.02.014
[Indexed for MEDLINE]

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