Abstract
The human intestinal lumen represents one of the most densely populated microbial niches in the biological world and, as a result, the intestinal innate immune system exists in a constant state of stimulation. A key component in the innate defence system is the intestinal epithelial layer, which acts not only as a physical barrier, but also as an immune sensor. The expression of pattern recognition receptors, such as Toll-like receptors, in epithelial cells allows innate recognition of a wide range of highly conserved bacterial moieties, termed microbial-associated molecular patterns (MAMPs), from both pathogenic and non-pathogenic bacteria. To date, studies of epithelial immunity have largely concentrated on inflammatory pathogenic antigens; however, this review discusses the major types of MAMPs likely to be produced by the enteric bacterial microbiota and, using data from in vitro studies, animal model systems and clinical observations, speculates on their immunomodulatory potential.
Highlights
The intestine represents the body’s largest mucosal surface, with the adult human intestine estimated to cover an area of about 250 m2 (Artis, 2008)
Due to the vast expanse of intestinal tissue exposed to the microbiota, the local innate immune system is in a constant state of stimulation, and a chronic, low-level proinflammatory response is characteristic of enteric immune homeostasis (Macpherson & Harris, 2004; Artis, 2008)
Human intestinal epithelial cell lines (HT29, Caco-2 and T84 cells) were subsequently shown to constitutively express Toll-like receptors (TLR)-9 mRNA, the upregulation of which was stimulated by pathogenic CpG-DNA (Akhtar et al, 2003)
Summary
The intestine represents the body’s largest mucosal surface, with the adult human intestine estimated to cover an area of about 250 m2 (Artis, 2008). Epithelium-associated, enteric immune cells, such as macrophages, dendritic cells, T-cells and B-cells, differentially express two major groups of PRRs, the cell surface Toll-like receptors (TLRs) and the intracellular nucleotide-binding oligomerization domain (NOD) receptors (Hornung et al, 2002; Iwasaki & Medzhitov, 2004; Akira et al, 2006). Human intestinal epithelial cell lines (HT29, Caco-2 and T84 cells) were subsequently shown to constitutively express TLR-9 mRNA, the upregulation of which was stimulated by pathogenic CpG-DNA (Akhtar et al, 2003). Akhtar et al (2003) showed an increased secretion of the proinflammatory IL-8 by intestinal epithelial cells in response to CpG-DNA It was subsequently suggested by Dalpke et al (2006) that stimulation of TLR-9 would be difficult in vivo, limiting the physiological importance of TLR-9.
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