Signal Transduction in the Intestinal Mucosa

This chapter considers the remarkable signal transduction networks that have evolved between intestinal microbes and their host in trying to maintain the balance of health and disease. Resident bacteria serve a central line of resistance to colonization by exogenous microbes and thus assist in preventing the potential invasion of the intestinal mucosa by an incoming pathogen. A number of enteric pathogens and some opportunistic commensal bacteria possess the means to provoke NF-κB activation and, subsequently, intestinal inflammation. Innate epithelial defense mechanisms provide a rapid response whereby microbial pathogens in the host are quickly detected and signals are generated that activate mucosal antimicrobial defense mechanisms. The intimate interaction between enteropathogenic Escherichia coli (EPEC) and the intestinal epithelium causes the induction of phosphate fluxes within the host cells, as well as the activation of protein kinase C (PKC), phospholipase C, and NF-κB. Chloride secretion in the intestinal mucosa involves the collaborative effort of several transporters. The current paradigm postulates that intestinal epithelial cells respond to Salmonella enterica serovar Typhimurium by the polarized release of distinct proinflammatory chemoattractants, which sequentially orchestrate neutrophil movement across the intestinal epithelium. Speculatively, microorganisms intimately associated with the intestinal mucosa may have evolved such mechanisms to dampen the host proinflammatory and immune responses without provoking apoptotic death. A more complete understanding of the signal transduction cascades that exist between the intestinal bacteria and the human host in the intestinal mucosa may uncover new insights into human diseases and reveal novel approaches to treating them.