Role of Toll-Like Receptors in Innate Immunity of the Intestine

Abstract

The pre-epithelial mucous layer at the apical epithelial surface-consisting of mucin glycoproteins, trefoil peptides, and, in the small intestine, defensins-significantly contributes to efficient protection of the underlying host. Toll-like receptors (TLR) are found expressed by many cell types throughout the whole gastrointestinal tract in vitro and in vivo, e.g., several intestinal epithelial cells (IEC) lines of the small intestine and colon, gastric pit cells, fetal intestinal cells, intestinal macrophages of the lamina propria, and intestinal myofibroblasts. Mammalian TLR may enable IEC to participate in innate immunity to microbial pathogens in at least four ways: (i) recognition of molecular patterns present on commensals and pathogens; (ii) expression at the interface with the “environment” of the gastrointestinal lumen; (iii) induction of secretion of pro-or anti-inflammatory cytokines and chemokines that link to the adaptive immune system; and (iv) induction of antimicrobial effector pathways. The chapter talks about alteration of TLR expression in human inflammatory bowel disease (IBD), and TLR dysregulation in infectious diseases. Future research will identify further TLR ligands, specify interconnective signaling cascades activated by TLR, and clarify the potential role of intestinal epithelial TLR in the pathogenesis of IBD and other aberrant inflammatory processes in the gastrointestinal tract. Identifying the physiological mechanisms through which intestinal TLR and other pattern-recognition receptors (PRR) modulate host defense in the gastrointestinal tract could lead to new therapeutic approaches to combat microbial associated gastrointestinal disorders, such as infectious diseases and perhaps IBD.