Epithelial barrier: an interface for the cross‐communication between gut flora and immune system

Abstract

Large numbers of environmental antigens, including commensal bacteria and food-derived antigens, constitutively interact with the epithelial layer of the gastrointestinal (GI) tract. Commensal bacteria peacefully cohabit with the host GI tract and exert multiple beneficial or destructive effects on their host. Intestinal epithelial cells (IECs) constitute the first physical and immunological protective wall against invasive pathogens and a cohabitation niche for commensal bacteria. As the physiological homeostasis of IECs is maintained by multiple biological processes such as apoptosis, autophagy, and the handling of endoplasmic reticulum stress, the aberrant kinetics of these biological events, which have genetic and environmental causes, leads to the development of host intestinal pathogenesis such as inflammatory bowel disease. In addition, IECs recognize and interact with commensal bacteria and give instructions to mucosal immune cells to initiate an immunological balance between active and quiescent conditions, eventually establishing intestinal homeostasis. The mucosal immune system regulates the homeostasis of gut microbiota by producing immunological molecules such as secretory immunoglobulin A, the production of which is mediated by IECs. IECs therefore play a central role in the creation and maintenance of a physiologically and immunologically stable intestinal environment.

Microbiote intestinal et développement du système immunitaire

“…Cette régulation dynamique de la réponse épithéliale est contrôlée par de nombreux récepteurs pour des motifs microbiens, tels que les récepteurs Toll-like et NOD (nucleotide oligomerization domain)-like qui, en activant notamment la voie NF-B (nuclear factor-kappaB), stimulent la transcription de peptides antimicrobiens [3] mais aussi la production de chimiokines et de cytokines qui favorisent le recrutement et l'activation de phagocytes, de cellules dendritiques et de lymphocytes qui renforcent et complètent la barrière épithéliale (voir plus loin). Cette signalisation fait l'objet d'une régulation très précise [6]. En effet, l'inactivation de la voie NF-B dans les cellules épithéliales, tout comme son activation excessive, provoquent des colites inflammatoires sévères, aggravées ou déclenchées par le microbiote.…”

“…En effet, l'inactivation de la voie NF-B dans les cellules épithéliales, tout comme son activation excessive, provoquent des colites inflammatoires sévères, aggravées ou déclenchées par le microbiote. Cependant, certaines bactéries commensales, spécialement dans le côlon, produisent des facteurs solubles comme des acides gras à chaîne courte, qui freinent l'activation de la voie NF-B dans les cellules épithéliales et évitent l'emballement des réponses inflammatoires délétères tant pour l'hôte que pour les bactéries [6]. Une réponse inflammatoire excessive peut en effet favoriser la sélection de bactéries pathogènes au détriment des bactéries commensales, réduire leur diversité ou induire des déséquilibres (dysbiose) entre espèces [7].…”

Probiotics, antibiotics and the immune responses to vaccines

“…Commensal bacteria influence the epithelial barrier in many ways; structural components and metabolites of the intestinal microbiota act on IECs and local innate leucocytes to maintain barrier integrity and regulate immune homeostasis [49]. Microbiota-derived short-chain fatty acids (SCFA), a by-product of metabolism, are important mediators in the cross-talk between the microbiota and IEC, and studies in animals indicate a role in prevention of inflammation [50] that is also reflected in the finding of fewer butyrateproducing bacteria in patients with inflammatory bowel disease [51].…”

Interaction exists between matriptase inhibitors and intestinal epithelial cells

“…Intestinal epithelium as a defense barrier can protect the gastrointestinal tract from the invasion of enteropathogenic bacteria, and restricts the absorption of various harmful chemical substances into the bloodstream [1][2][3] . The increased paracellular permeability of intestinal epithelial cell (IEC) layer indicates a damaged barrier function after enterocytes were exposed to adverse stimuli, such as oxidative stress 4 .…”