Abstract
The intestinal mucosa faces the challenge of regulating the balance between immune tolerance towards commensal bacteria, environmental stimuli and food antigens on the one hand, and induction of efficient immune responses against invading pathogens on the other hand. This regulatory task is of critical importance to prevent inappropriate immune activation that may otherwise lead to chronic inflammation, tissue disruption and organ dysfunction. The most striking example for the efficacy of the adaptive nature of the intestinal mucosa is birth. Whereas the body surfaces are protected from environmental and microbial exposure during fetal life, bacterial colonization and contact with potent immunostimulatory substances start immediately after birth. In the present review, we summarize the current knowledge on the mechanisms underlying the transition of the intestinal mucosa during the neonatal period leading to the establishment of a stable, life-long host–microbial homeostasis. The environmental exposure and microbial colonization during the neonatal period, and also the influence of maternal milk on the immune protection of the mucosa and the role of antimicrobial peptides, are described. We further highlight the molecular mechanisms of innate immune tolerance in neonatal intestinal epithelium. Finally, we link the described immunoregulatory mechanisms to the increased susceptibility to inflammatory and infectious diseases during the neonatal period.
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Acknowledgments
S.S. was recipient of an APART fellowship at the Institute for Medical Microbiology at Hanover Medical School. S.S. present address is: Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Vienna, Austria. C.C. was supported by a post-doctoral fellowship from the Alexander Von Humboldt foundation. M.W.H. was supported by the German Research Foundation (Ho2236/5-3), the Federal Ministry of Education and Research (DLR 01GU0825) as well as the Collaborative Research Center SFB 621 and SFB900.
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Stockinger, S., Hornef, M.W. & Chassin, C. Establishment of intestinal homeostasis during the neonatal period. Cell. Mol. Life Sci. 68, 3699–3712 (2011). https://doi.org/10.1007/s00018-011-0831-2
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DOI: https://doi.org/10.1007/s00018-011-0831-2