Interactions of the Intestinal Epithelium with the Pathogen and the Indigenous Microbiota: A Three-Way Crosstalk
Figure 1
(a) Healthy epithelial
surface. A healthy intestinal epithelial surface acts as a physical and biochemical
barrier with key features including the
apical brush border, the mucus layer, the presence of antimicrobial peptides
(blue black dots) in the lumen, the glycocalyx, and the epithelial tight
junctions. Also seen in the illustration are numerous commensal bacteria and a
dendritic cell sampling the lumen with its extended dendrites (yellow). (b) Key features of S. typhimurium infected epithelium. Such
host pathogen interactions involve translocation of bacterial effectors (green
circles) into the epithelial cells, membrane ruffling, bacterial endocytosis,
and SCV formation. Chemoatractants are secreted by the epithelial surface that
leads to PMN influx. SCV: Salmonella containing vacuole. (c) Intestinal epithelial
surface of an antibiotic-treated patient showing enrichment of a set of
antibiotic resistant members of the commensal microflora (light blue and brown)
such as C. difficle and E. faecalis. The C. difficle proteins, TcdA and Tcdb (red circles) act
intracellularly as glycosyltransferases and inhibit Rho, Rac, and Cdc42. The
effect of these modifications lead to actin condensation, transcriptional
activation of several genes and apoptosis. Other mechanisms that are triggered
include basolateral IL8 secretion, apical Hepoxillin A synthesis, and PMN
influx in the apical surface.