Elsevier

Seminars in Immunology

Volume 19, Issue 2, April 2007, Pages 106-115
Seminars in Immunology

Review
The intestinal epithelial barrier: How to distinguish between the microbial flora and pathogens

https://doi.org/10.1016/j.smim.2006.12.006Get rights and content

Abstract

The gastrointestinal tract is fundamental for the uptake of nutrients and fluids, but it also represents the greatest surface of the body in contact with the external environment and most human pathogens enter the body through the mucosal surface, especially in the intestine. The intestinal immune system protects the sterile core of the organism against invasion and systemic dissemination of both pathogens and limits for level penetration of commensal microorganisms. In addition, the human intestine is continually in contact with 1014 commensal bacteria containing more than 500 different species. These commensal bacteria confer health benefits to their host by helping dietary digestion, development of gut immunity and preventing colonization by pathogens. To maintain integrity and normal function of intestine, a delicate equilibrium must be reached between the bacterial flora and intestinal immune system. This review discusses the recent advances in our understanding of how the mucosal intestinal barrier maintains a local homeostatic response to the resident intestinal bacteria, while protecting the host against enteric pathogens. In particular, the emerging function of Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in controlling mucosal immunity will be presented.

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.

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