Bacteria--Mast Cell Interactions in Inflammatory Disease

Abstract

Chronic inflammatory diseases of the gastrointestinal tract such as ulcerative colitis and Crohn's disease are characterized by mast cell proliferation and secretion of inflammatory mediators. The determinant(s) responsible for stimulating mast cells in the intestinal mucosa is not known. We investigated the interaction of mast cells with type 1 fimbriated Escherichia coli, an opportunistic pathogen and a constituent of the normal indigenous microflora of the gut. Unlike a mutant derivative deficient in the FimH subunit of the fimbriae or nonfimbriated E. coli, type 1 fimbriated E. coli adhered avidly to mast cells. As a consequence of this interaction, the mast cells phagocytozed and killed adherent bacteria. The mast cell bactericidal activity involved generation of superoxide anion and acidification of phagocytic vacuoles. In addition, many of the mast cells had degranulated and released inflammatory mediators such as histamine. These observations have implications both for normal host defense and for the initiation and perpetuation of inappropriate inflammatory responses in the gastrointestinal tract.