Although mast cells have been implicated in a variety of inflammatory conditions including immediate hypersensitivity and interstitial cystitis, their physiological role in the body is unknown. We investigated the role of mast cells in host defence against bacterial infections using a well characterized mast-cell-deficiency mouse model. We report here that mast cells, which are selectively located at portals of bacterial entry, are important to host defence. Mast-cell-deficient WBB6F1-W/Wv mice (W/Wv) were up to 20-fold less efficient in clearing enterobacteria than control WBB6F1 +/+ (+/+) mice or mast-cell-reconstituted W/Wv (W/Wv+MC) mice. With higher bacteria inocula, only W/Wv mice died (80%). The limited bacterial clearance in W/Wv mice directly correlated with impaired neutrophil influx. The mast-cell chemoattractant TNF-alpha was implicated in the neutrophil response because TNF-alpha was locally released only in +/+ and W/Wv+MC mice, TNF-alpha-specific antibodies blocked over 70% of the neutrophil influx, and purified mast cells released TNF-alpha upon incubation with bacteria. Additionally, the type-1 fimbrial subunit, FimH, was the necessary enterobacterial component for mast-cell activation and neutrophil influx because an isogenic FimH- mutant evoked a limited neutrophil response in +/+ mice compared to wild-type bacteria.

The strategic location of mast cells at the host-environment interface and their ability to release potent mediators of inflammation have suggested that these cells may play a pivotal role in host defense against bacterial infection. The ability of the opportunistic pathogen, Escherichia coli, to induce degranulation of mast cells obtained from the mouse peritoneum was investigated. We determined that unlike a mutant derivative deficient in the FimH subunit of the fimbriae or nonfimbriated E. coli, type 1 fimbriated E. coli induced mast cell degranulation in vitro. The magnitude of mast cell degranulation was directly proportional to the number of adherent bacteria on the cell surface in the initial period of the interaction. Using a mouse model of bacterial peritonitis, we demonstrated mast cell degranulation and histamine release by type 1 fimbriated bacteria in vivo. Furthermore, beads coated with FimH but not with FimA, the major subunit of type 1 fimbriae, evoked mast cell release of histamine in vivo in amounts comparable to that elicited by type 1 fimbriated E. coli. These studies reveal that mast cells can be degranulated by interaction with type 1 fimbriated E. coli and that FimH, the mannose-binding component of the fimbriae, is a potent mast cell stimulant. (J. Clin. Invest. 1994.

Recent studies have implicated rodent mast cells in the innate immune response to infectious bacteria. We report that cord blood-derived human mast cells (CBHMC) obtained from culture of cord blood progenitors phagocytozed and killed various gram-negative and gram-positive bacteria and simultaneously released considerable amounts of tumor necrosis factor alpha. Overall, the extent of the endocytic and exocytic response of CBHMC correlated with the number of adherent bacteria. Thus, human mast cells are intrinsically capable of mediating microbial recognition and of actively contributing to the host defense against bacteria.