Epithelial barrier biology: good fences make good neighbours

Abstract

The external surfaces of the body, such as the skin and the gastrointestinal mucosal membrane, are an important line of defence preventing the invasion of microorganisms and their products. Mucosal immune cells, especially intraepithelial lymphocytes, are involved in maintaining the integrity of these epithelial barriers. They contribute towards the tolerance to commensal organisms, which occupy these same sites, and to the immune responses against harmful organisms and their products. The composition of the microbiota is influenced by immune cells as well as external environmental factors, especially the use of antibiotics and diet. There is an increasing appreciation that the microbiota affects systemic immune responses in addition to local immunity. Failure to control the occupancy by microorganisms may result in the disruption of the delicate homeostasis between beneficial and harmful microorganisms and contribute to inflammatory pathologies. This review will discuss some of our current understanding of the impact of immune cells and diet on the microbiota.

Figure 1

Structural organization of intestinal mucosa. Schematic representation of the small intestinal mucosal barrier, consisting of a mucosal layer (1) and gradients of IgA and antimicrobial factors, the epithelial cells (2) made up of enterocytes, Paneth cells, goblet cells and enteroendocrine cells, intraepithelial lymphocytes (3), and the lamina propria (4). Additional secondary lymphoid structures, such as cryptopatches and Peyers’ patches are present in the lamina propria.

Figure 2

Influences affecting the intestinal microbial composition and barrier homeostasis. Besides host genetics, chance encounters, stress and aging effects, the diet has a major influence on the intestinal microbial composition. Especially the fibre content, and their metabolic products such as short chain fatty acids (SCFA), acetate, propanoate and butyrate have a major impact on the mutually beneficial relationship (symbiosis) between the host and the microbiota. In addition, microbial factors such as polysaccharide A (PSA) and peptidoglycans (PTGN) make a direct contribution this relationship. Alterations in the microbial make up, dysbiosis, may result in epithelial barrier damage and stress as the result of a reduction in protective microbial factors and an increase in pathogenic microorganisms.

Figure 3

Maintaining the ‘fence’. Balancing epithelial barrier health via cross-talk between epithelial cells and the luminal microorganisms, and the cells of the immune system, especially intraepithelial lymphocytes (IELs), themselves maintained via dietary derived aryl hydrocarbon receptor (AhR) ligands such as indole-3-carbinol (I3C). The IELs maintain the epithelial barrier via release of growth factors and support in the activation of antimicrobial peptides. Upon barrier breakthrough, IELs are directly involved in the cytolytic immune response, removing infected cells, and orchestrating subsequent adaptive immunity as well as the barrier repair response.