APOPTOSIS OF HUMAN INTESTINAL EPITHELIAL-CELLS AFTER BACTERIAL INVASION

Epithelial cells that line the human intestinal mucosa are the initial site of host invasion by bacterial pathogens. The studies herein defi ne apoptosis as a new category of intestinal epithelial cell response to bacterial infection. Human colon epithelial cells are shown to unde rgo apoptosis following infection with invasive enteric pathogens, suc h as Salmonella or enteroinvasive Escherichia coli. In contrast to the rapid onset of apoptosis seen after bacterial infection of mouse mono cyte-macrophage cell lines, the commitment of human intestinal epithel ial cell lines to undergo apoptosis is delayed for at least 6 h after bacterial infection, requires bacterial entry and replication, and the ensuing phenotypic expression of apoptosis is delayed for 12-18 h aft er bacterial entry. TNF-alpha and nitric oxide, which are produced as components of the intestinal epithelial cell proinflammatory program i n the early period after bacterial invasion, play an important role in the later induction and regulation of the epithelial cell apoptotic p rogram. Apoptosis in response to bacterial infection may function to d elete infected and damaged epithelial cells and restore epithelial cel l growth regulation and epithelial integrity that are altered during t he course of enteric infection. The delay in onset of epithelial cell apoptosis after bacterial infection may be important both to the host and the invading pathogen since it provides sufficient time for epithe lial cells to generate signals important for the activation of mucosal inflammation and concurrently allows invading bacteria time to adapt to the intracellular environment before invading deeper mucosal layers .