Microbial Exposure During Early Life Has Persistent Effects on Natural Killer T Cell Function

By T. Olszak, Dingding An, S. Zeissig, M. P. Vera, J. Richter, Andre Franke, J. Glickman, R. Siebert, R. Baron, Dennis L. Kasper and 1 more. Science, 2012

1,587 citations recorded by the source corpus.

Microbes: Early and Often Epidemiological studies have suggested that the increase in the incidence of asthma and other inflammatory diseases seen in many parts of the world may be due to a reduced exposure to microbes during early childhood. Olszak et al. (p. 489, published online 22 March) now show that commensal microflora help to regulate the numbers and functions of natural killer T (NKT) cells in the colon and lung in mice. Germ-free mice had elevated numbers of NKT cells in these tissues and were more susceptible to chemically induced colitis and allergic asthma. Neonatal recolonization of germ-free mice with microflora prevented enhanced colitis and asthma sensitivity; however, exposure of adult mice to these conditions was not effective. Thus, early exposure to microbes has important, lasting effects on the immune system's sensitivity to inflammation. Early exposure of germ-free mice to microbes keeps later inflammation in check by modulating immune cells. Exposure to microbes during early childhood is associated with protection from immune-mediated diseases such as inflammatory bowel disease (IBD) and asthma. Here, we show that in germ-free (GF) mice, invariant natural killer T (iNKT) cells accumulate in the colonic lamina propria and lung, resulting in increased morbidity in models of IBD and allergic asthma as compared with that of specific pathogen-free mice. This was associated with increased intestinal and pulmonary expression of the chemokine ligand CXCL16, which was associated with increased mucosal iNKT cells. Colonization of neonatal—but not adult—GF mice with a conventional microbiota protected the animals from mucosal iNKT accumulation and related pathology. These results indicate that age-sensitive contact with commensal microbes is critical for establishing mucosal iNKT cell tolerance to later environmental exposures.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/8e6ba8ea10445bf7311e4ae2d6eeb8de1b058da7

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. Y. Belkaid
2. O. Harrison
3. Yan Wang
4. L. Kasper
5. J. Mora
6. D. Mathis
7. K. Papadakis
8. Rob Knight

Citations in the corpus

• Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer (2016, positive): “Early interaction with commensal microbes is essential for healthy immune development and metabolic programming, and aberrant microbial colonization in newborns has been associated with long-term effects on host metabolism 3 or impaired immune development 2 .”
• International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors (2014, neutral): “Recent work suggests that CXCR6/CXCL16 are important for regulating NKT cell accumulation in colon and lung in mice and that CXCL16 expression at these sites is downregulated by neonatal colonization with bacterial flora (Olszak et al., 2012).”
• Maturation of the Infant Microbiome Community Structure and Function Across Multiple Body Sites and in Relation to Mode of Delivery (2017, neutral): “Reintroducing microorganisms post-natally (after birth) partially corrects many of these defects, though even a brief GF neonatal period can induce immunological changes that persist into adulthood 12,14 .”
• Defining dysbiosis and its influence on host immunity and disease (2014, background): “Interestingly, the development of these cell types is dynamically regulated by the microbiota such that GF mice have elevated numbers of these cells within the gut (Olszak et al., 2012).”