ReviewThe intestinal epithelial barrier: How to distinguish between the microbial flora and pathogens
Section snippets
Mechanisms of mucosal protection
Many different cell types, including members of the innate and the adaptive immune systems, specialized epithelial and mesenchymal cells constantly interact with microorganisms at the level of the gut lumen, epithelium and lamina propria [1], [2], [3], [4]. Innate immunity provides broad protection against microbes without previous contact. These mechanisms of defence are aimed at preventing microorganisms from gaining access to the apical surface of the epithelial cell layer, which provide a
What distinguishes commensals from pathogens
Commensal bacteria in the gut tract constitutes a heterogenous microbial ecosystem containing approximately 1014 bacteria [15] The commensal bacteria mainly reside in the lumen outside the mucus layer. Commensal bacteria are composed of anaerobic, aerobic and facultative aerobic bacteria. It has been estimated that there are more or less 500 commensal bacterial species in the intestine. However, because most of these bacteria are difficult to culture in vitro, only 20–40% of the bacterial
The host surveillance system for microorganisms: TLRs and NLRs
When bacteria breach the glycocalyx, mucins, IgA and antimicrobial peptide defences, they enter into close contact with epithelial cells that line the intestine. The gut epithelium directly senses commensal and pathogens through the innate immune system. This recognition is mediated by a variety of germ line-encoded pattern recognition receptors (PRRs) also called pattern recognition molecules (PRMs). These PRMs specifically recognize essential invariant molecular constituents of microbes, in
Host responses to commensals
The gut is home to a large collection of microorganisms, and its global composition varies along the intestinal tract and between individuals. This results from the co-evolution between microbial communities and their hosts [79], [80], [81]. The human intestinal microbiota collective genome (microbiome) contains more than 100 times the number of genes found in the human genome, and this genetic material, even though not controlled directly by the human host itself, contributes strongly to the
Host responses to bacterial pathogens
The host response to pathogens primarily relies on the detection of the intruder by the host's pattern recognition molecules, among which TLRs and NLRs have been shown to play a crucial role (see above). The microbial motifs that trigger the activation of PRMs are globally conserved between pathogenic and non-pathogenic microbes, but what generally distinguishes these two classes of microbes is the fact that pathogen interaction with its host results in the activation of a strong innate immune
Conclusions
The intestinal mucosal surface is the center stage of a permanent ballet of microbes interacting with the host epithelium. A long-standing co-evolution between the host and the resident commensal flora has resulted in a complex ecosystem. In this tissue, more than any other, immune homeostasis is a permanent challenge, struggling between the necessity of preserving the microbial flora and protecting the widest mucosal surface of the host from pathogenic intruders. The difficulty in maintaining
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Present address: Department of Immunology, University of Toronto, Toronto, Canada.