The impact of perinatal immune development on mucosal homeostasis and chronic inflammation

Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps University Marburg, Medical Faculty, Baldingerstrasse, 35043 Marburg, Germany.
Nature Reviews Immunology (Impact Factor: 33.84). 12/2011; 12(1):9-23. DOI: 10.1038/nri3112
Source: PubMed

ABSTRACT The mucosal surfaces of the gut and airways have important barrier functions and regulate the induction of immunological tolerance. The rapidly increasing incidence of chronic inflammatory disorders of these surfaces, such as inflammatory bowel disease and asthma, indicates that the immune functions of these mucosae are becoming disrupted in humans. Recent data indicate that events in prenatal and neonatal life orchestrate mucosal homeostasis. Several environmental factors promote the perinatal programming of the immune system, including colonization of the gut and airways by commensal microorganisms. These complex microbial-host interactions operate in a delicate temporal and spatial manner and have an important role in the induction of homeostatic mechanisms.

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    • "The pace of development of endogenous SIgA production is highly variable in human infants, and may take several years to achieve adult levels. such as microbial load in the intestine [63]. In developed countries, it may take several years before the concentrations of intestinal SIgA achieve adult levels. "
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    ABSTRACT: Secretory IgA (SIgA) antibodies in the intestinal tract form the first line of antigen-specific immune defense, preventing access of pathogens as well as commensal microbes to the body proper. SIgA is transported into external secretions by the polymeric immunoglobulin receptor (pIgR). Evidence is reported here that the gut microbiota regulates production of SIgA and pIgR, which act together to regulate the composition and activity of the microbiota. SIgA in the intestinal mucus layer helps to maintain spatial segregation between the microbiota and the epithelial surface without compromising the metabolic activity of the microbes. Products shed by members of the microbial community promote production of SIgA and pIgR by activating pattern recognition receptors on host epithelial and immune cells. Maternal SIgA in breast milk provides protection to newborn mammals until the developing intestinal immune system begins to produce its own SIgA. Disruption of the SIgA-pIgR-microbial triad can increase the risk of infectious, allergic and inflammatory diseases of the intestine.
    Immunology Letters 12/2014; 162(2). DOI:10.1016/j.imlet.2014.05.008 · 2.37 Impact Factor
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    • "The impact of the microbiota on gut physiology , metabolism, and health has been shown to be largely influenced by microbial activities, like fermentation of food components not digested by the upper gastrointestinal tract such as nondigestive carbonate [55]. Interaction between host and bacteria in the gut mucosa is, of course, essential for host digestive efficiency and intestinal physiology, and plays a major role in the establishment of immune postnatal tolerance after birth, as well as in the maturation of the gut-associated lymphoid tissue [27] [56] [57]. Doubtlessly, the microbiota and the immune system of the host interact in a two-way street: while bacteria induce immune maturation, the host immune system regulates the number and the composition of the bacteria. "
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    ABSTRACT: The intestinal tract is engaged in a relationship with a dense and complex microbial ecosystem, the microbiota. The establishment of this symbiosis is essential for host physiology, metabolism, and immune homeostasis. Because newborns are essentially sterile, the first exposure to microorganisms and environmental endotoxins during the neonatal period is followed by a crucial sequence of active events leading to immune tolerance and homeostasis. Contact with potent immunostimulatory molecules starts immediately at birth, and the discrimination between commensal bacteria and invading pathogens is essential to avoid an inappropriate immune stimulation and/or host infection. The dysregulation of these tight interactions between host and microbiota can be responsible for important health disorders, including inflammation and sepsis. This review summarizes the molecular events leading to the establishment of postnatal immune tolerance and how pathogens can avoid host immunity and induce neonatal infections and sepsis.
    Clinical and Developmental Immunology 05/2013; 2013:270301. DOI:10.1155/2013/270301 · 2.93 Impact Factor
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    • "It is widely known that, to achieve neonatal mucosal tissue homeostasis, the gut needs to develop tolerance to ingested antigens and to components of the indigenous bacterial microbiota. Neonatal defects in establishing tolerance have been linked to the development of disease and chronic inflammation of the mucosa (Renz et al., 2011). In addition, studies performed in germ-free mice have taught us that early life colonisation is required for the development of a fully functional immune system and affects many physiological processes within the host (Smith et al., 2007). "
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    ABSTRACT: The presence of bacteria in human milk has been acknowledged since the seventies. For a long time, microbiological analysis of human milk was only performed in case of infections and therefore the presence of non-pathogenic bacteria was yet unknown. During the last decades, the use of more sophisticated culture-dependent and -independent techniques, and the steady development of the -omic approaches are opening up the new concept of the 'milk microbiome', a complex ecosystem with a greater diversity than previously anticipated. In this review, possible mechanisms by which bacteria can reach the mammary gland (contamination versus active migration) are discussed. In addition, the potential roles of human milk for both infant and maternal health are summarised. A better understanding of the link between the milk microbiome and health benefit, the potential factors influencing this relationship and whether or not it can be influenced by nutrition is required to open new avenues in the field of pregnancy and lactation.
    Beneficial Microbes 12/2012; 4(1):17-30. DOI:10.3920/BM2012.0040 · 1.50 Impact Factor
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