Molecular and cellular mechanisms of tissue invasion by Shigella flexneri

Shigella flexneri, a member of the family of enterobacteriaceae, causes bacillary dysentery by invading the human colonic mucosa and provoking a very intense inflammation. Recent in vitro data allow us to integrate different phenomena into a model of the infectious process during shigellosis. In vivo, bacteria appear to enter the submucosa via the M cells, specialized cells that cover the follicular structures of the intestinal mucosa. Once inside the submucosa, shigellae encounter resident tissue macrophages, which are infected, and apoptosis is rapidly induced. During programmed cell death the inflammatory cytokine interleukin-1 (IL-1) is released. Interleukin-1 triggers an inflammatory reaction characterized by extravasation of polymorphonuclear (PMN) cells. The inflammation is probably potentiated by the production of other cytokines by epithelial, endothelial, and PMN cells. Polymorphonuclear cells migrate through the epithelium into the lumen of the colon, destabilizing the integrity of the epithelial barrier. The damaged epithelium allows massive entry of bacteria into the submucosa. Further colonization of the epithelium aggravates inflammation, which in turn causes extensive tissue destruction. Both the in vitro and in vivo results that support this model are discussed.