Abstract:
Mast cells have long been acknowledged as the major effector cells of allergic reactions because they possess the high-affinity IgE receptor (Fc?RI), which mediates the release of many inflammatory mediators such as histamine, leukotriene and prostaglandin when crosslinked by antigens. Whereas, mast cells are located at the host-environment interface, including the skin, respiratory system, and gastrointestinal tract. Recently, it has been revealed that mast cells share many features with primary effector cells that belong to the innate immune system. As well, some investigators have demonstrated that mast cell-deficient W/Wv mice display increased mortality compared with wild-type mice using a model of acute septic peritonitis induced by cecal ligation and perforation (CLP) and that the lethal effects of CLP are prevented by the adoptive transfer of bone marrow-derived mast cells into the peritoneal cavity. Indicating that mast cells are involved in one of the principal members of the innate immune system. However, the changes in the behavior of mast cells following infectious diseases remain unclear. We investigated the effects of infection on the expression of surface receptors and uptake of microbes by mast cells, using bacterial components, and studied the change in cytokine production in mast cells after bacterial uptake.
The change of mRNA expression for Fc?RI was studied using RT-PCR and real-time PCR. The changes of surface expression of Fc?RI were examined using flow cytometry, and degranulation mediated by Fc?RI aggregation was determined by ?-Hexosaminidase release assay.
Treatment of lipoteichoic acid (LTA) decreased the expression of Fc?RI? mRNA on human mast cells. Peptidoglycan (PGN) up-regulated Fc?RI? mRNA, but down-regulated that of Fc?RI??, an amplifier of the surface expression of Fc?RI?. Both LTA and PGN diminished surface expression of Fc?RI on mast cells detectable by flow cytometry. As well, they also reduced mast cells degranulation mediated by the treatment of antigen-specific IgE. Complement receptor 3, which is closely related to phagocytose bacteria by mast cells, expression was augmented by LTA but not by PGN or 3CpG-oligodeoxynucleotide. LTA also enhanced the uptake of opsonized bacteria. After bacterial internalization, mast cells augmented the production of pre-inflammatory cytokines, while Th1 and Th2 cytokine production showed no change.
These results indicate that bacterial infections direct human mast cells function towards innate immunity and away from allergic reaction. Applying current knowledge, bacterial components especially TLR2 ligands give new impetus to anti-allergic drug development.