Beth A. McCormick^1,2, Samuel I. Miller³, and James L. Madara^1,2.

¹ Departments of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115

² The Harvard Digestive Diseases Center

³ Departments of Medicine and Microbiology, University of Washington, Seattle, WA 98195.

Received 06/19/96; Accepted 07/09/96; On-line 08/01/96

2. INTRODUCTION

Salmonella typhimurium is the most common serotype isolated from humans suffering from infectious gastroenteritis and correspondingly has long been recognized as a public health problem. Contact between the epithelial cell apical membrane elicits a variety of epithelial responses. Such epithelial responses are likely triggered by specific contact-dependent, bacterial derived signals which are themselves modulated by physical characteristics of the microenvironment such as oxygen tension and osmolarity (1-5). Subsequent to such alterations, Salmonella may be internalized in a membrane bound vacuole and may translocate across the intestinal epithelium (6-7). The details of how such Salmonella-intestinal epithelial contacts evoke the classical histogical lesion of neutrophil transepithelial migration are incomplete (7-10). However, it is clear that transepithelial migration of neutrophils occurs early after Salmonella and epithelial contact (7), and well before the epithelium loses its structural integrity (8). Such observations, however, imply that contact between the bacterial outer membrane and the epithelial apical membrane results in the generation of signals which directs the subsequent trafficking of neutrophils. Thus, current paradigm suggests that the host cell plays an active role in both Salmonella internalization, as well as in the orchestration of inflammatory responses. What follows is a brief review of the molecular pathways used by Salmonella in epithelial cell binding which govern the mechanisms of Salmonella internalization and the promotion of intestinal inflammation.