REVIEW

Intestinal epithelial responses to enteric pathogens: effects on the tight junction barrier, ion transport, and inflammation

J Berkes, V K Viswanathan, S D Savkovic, G Hecht

Section of Digestive Diseases and Nutrition, University of Illinois at Chicago and Chicago Veterans Administration Medical Center (West Side Division), Chicago, IL, USA

Correspondence to:
Correspondence to:
Dr G Hecht, Section of Digestive Diseases and Nutrition, Department of Medicine, University of Illinois at Chicago, 840 S Wood Street; CSB Rm 738A (m/c716), Chicago, IL 60612, USA;
gahecht{at}uic.edu

The effects of pathogenic organisms on host intestinal epithelial cells are vast. Innumerable signalling pathways are triggered leading ultimately to drastic changes in physiological functions. Here, the ways in which enteric bacterial pathogens utilise and impact on the three major physiological functions of the intestinal epithelium are discussed: alterations in the structure and function of the tight junction barrier, induction of fluid and electrolyte secretion, and activation of the inflammatory cascade. This field of investigation, which was virtually non-existent a decade ago, has now exploded, thus rapidly expanding our understanding of bacterial pathogenesis. Through increased delineation of the ways in which microbes alter host physiology, we simultaneous gain insight into the normal regulatory mechanisms of the intestinal epithelium.

Keywords: tight junctions; enteric pathogens; ion transport; epithelium; inflammation

Abbreviations: TJ, tight junctions; TER, transepithelial electrical resistance; PKC, protein kinase C; PKC, protein kinase C; PKCß, protein kinase Cß; EPEC, entero-pathogenic Escherichia coli; MLCK, myosin light chain kinase; EHEC, enterohaemorrhagic Escherichia coli; BFT, B fragilis enterotoxin; Isc, short circuit current; HA/P, haemagglutinin protease; CPE, C perfringens enterotoxin; CPE-R, C perfringens enterotoxin receptor; CFTR, cystic fibrosis transmembrane conductance regulator; CaCC, calcium activated chloride channel; GC-C, guanylate cyclase C; ST, stable toxins; DAG, diacylglycerol; IP₃, inositol 1,4,5-trisphosphate; TDH, thermostable direct haemolysin; Gal-1R, galanin-1 receptor; LPS, lipopolysaccharide; NO, nitric oxide; NOS, nitric oxide synthase; iNOS, inducible NOS; EIEC, enteroinvasive E coli; PGE₂; prostaglandin E₂; PGHS, prostaglandin H synthase; COX-2, cyclooxygenase 2; TLR, toll-like receptor; MHC, major histocompatibility complex; IL, interleukin; PEEC, pathogen elicited epithelial derived chemoattractant; NFB, nuclear factor B; TNF-, tumour necrosis factor ; IB, inhibitory protein B; IKK, IB kinase; NIK, NFB inducing kinase; MAP, mitogen activated protein; MAPK, MAP kinase; MAPKKK, MAPK kinase kinase; MEK, MAP/ERK kinases; JNK, c-Jun NH2 terminal kinase; AP-1, activating protein 1; cag; cytotoxin associated antigen

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