Article Text

Download PDFPDF

BACTERIAL INTERACTIONS WITH CELLS OF THE INTESTINAL MUCOSA: TOLL-LIKE RECEPTORS AND NOD2
Free
  1. E Cario
  1. Correspondence to:
    Dr E Cario
    University Hospital of Essen, Division of Gastroenterology and Hepatology, Institutsgruppe I, Virchowstr 171; D-45147 Essen, Germany; elke.cariouni-essen.de

Statistics from Altmetric.com

SUMMARY

Toll-like receptors (TLR) and NOD2 are emerging as key mediators of innate host defence in the intestinal mucosa, crucially involved in maintaining mucosal as well as commensal homeostasis. Recent observations suggest new (patho-) physiological mechanisms of how functional versus dysfunctional TLRx/NOD2 pathways may oppose or favour inflammatory bowel disease (IBD). In health, TLRx signalling protects the intestinal epithelial barrier and confers commensal tolerance whereas NOD2 signalling exerts antimicrobial activity and prevents pathogenic invasion. In disease, aberrant TLRx and/or NOD2 signalling may stimulate diverse inflammatory responses leading to acute and chronic intestinal inflammation with many different clinical phenotypes.

INTRODUCTION

The intestinal mucosa must rapidly recognise detrimental pathogenic threats to the lumen to initiate controlled immune responses but maintain hyporesponsiveness to omnipresent harmless commensals. Charles Janeway Jr first suggested that so-called pattern recognition receptors (PRRs) may play an essential role in allowing innate immune cells to discriminate between “self” and microbial “non-self” based on the recognition of broadly conserved molecular patterns.1 Toll-like receptors (TLRs) which comprise a class of transmembrane PRRs play a key role in microbial recognition, induction of antimicrobial genes, and the control of adaptive immune responses. NODs (NOD1 and NOD2) are a structurally distinct family of intracellular PRRs which presumably in the context of microbial invasion subserve similar functions (fig 1). TLRs and NOD2 are widely expressed on various cell types of the gastrointestinal mucosa, participating in host defence against microbial pathogens in at least four ways:

Figure 1

 Toll-like receptor 4/nucleotide binding oligomerisation domain 2 (TLR4/NOD2) structure and inflammatory bowel disease associated common variants. (A) Mammalian TLRs are a family of type I transmembrane receptors which are all characterised by three common structural features, as exemplified for TLR4 here: a divergent ligand binding extracellular domain with multiple leucine rich repeats (LRR), a short transmembrane region and a highly homologous cytoplasmic …

View Full Text

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.