Bacterial-mucosal interactions in inflammatory bowel disease: an alliance gone bad

Abstract

The complex interaction of genetic, microbial, and environmental factors may result in continuous activation of the mucosal immune system leading to inflammatory bowel disease (IBD). Most present treatments for IBD involve altering or suppressing the aberrant immune response; however, the role of the intestinal microbiota in the pathophysiology of IBD is becoming more evident. The epithelial layer is essential for the proper functioning of the gastrointestinal tract, and its increased permeability to the luminal antigens may lead to the inflammatory processes and mucosal damage observed in IBD. Factors affecting the efficacy of the epithelial barrier include presence of pathogenic bacteria (e.g., Helicobacter spp.), presence of probiotic bacteria, availability of selected nutrients, and others. Defective function of the mucosal barrier might facilitate the contact of bacterial antigens and adjuvants with innate and adaptive immune cells to generate prolonged inflammatory responses. This review will briefly describe the complex structure of the epithelial barrier in the context of bacterial-mucosal interactions observed in human IBD and mouse models of colitis.

Figures

Fig. 1.

Structure of the epithelial membrane including nonraft membrane and a lipid raft. Lipid rafts are enriched with cholesterol and studded with proteins. GPI, glycosylphosphatidylinositol-anchored cell surface glycoproteins.

Fig. 2.

Structure of the mucosal barrier. Tight junctions link adjacent colon epithelial cells. The processes of dendritic cells pass between epithelial cells. The dendritic cells sample and process antigen material for presentation to other immune cells. Mucus produced by epithelial cells serves an additional physical barrier to prevent penetration of luminal antigens.

Fig. 3.

Colon histology in Helicobacter-infected and -noninfected IL-10−/− adult mice. The histological appearance of the cecum is shown for noninfected control mice (A) and mice coinfected with H. rodentium and H. typhlonius in the absence of treatment (B) or following treatment with a commercially available 4-drug anti-Helicobacter regimen (C). Untreated IL-10−/− mice infected with H. rodentium plus H. typhlonius had marked mucosal hyperplasia with prominent inflammatory infiltrates. The mucosal hyperplasia and infiltrates were totally abrogated by anti-Helicobacter treatment. All photomicrographs were taken at the same magnification; bar represents 100 μm.