Streptococcal H(2)O(2) inhibits IgE-triggered degranulation of RBL-2H3 mast cell/basophil cell line by inducing cell death

Mast cells and basophils are central players in allergic reactions triggered by immunoglobulin E (IgE). They have intracellular granules containing allergic mediators (e.g., histamine, serotonin, inflammatory cytokines, proteases and β-hexosaminidase), and stimulation by IgE-allergen complex leads to the release of such allergic mediators from the granules, that is, degranulation. Mast cells are residents of mucosal surfaces, including those of nasal and oral cavities, and play an important role in the innate defense system. Members of the mitis group streptococci such as Streptococcus oralis, are primary colonizers of the human oral cavity. They produce hydrogen peroxide (H(2)O(2)) as a by-product of sugar metabolism. In this study, we investigated the effects of streptococcal infection on RBL-2H3 mast cell/basophil cell line. Infection by oral streptococci did not induce degranulation of the cells. Stimulation of the RBL-2H3 cells with anti-dinitrophenol (DNP) IgE and DNP-conjugated human serum albumin triggers degranulation with the release of β-hexosaminidase. We found that S. oralis and other mitis group streptococci inhibited the IgE-triggered degranulation of RBL-2H3 cells. Since mitis group streptococci produce H(2)O(2), we examined the effect of S. oralis mutant strain deficient in producing H(2)O(2,) and found that they lost the ability to suppress the degranulation. Moreover, H(2)O(2) alone inhibited the IgE-induced degranulation. Subsequent analysis suggested that the inhibition of degranulation was related to the cytotoxicity of streptococcal H(2)O(2). Activated RBL-2H3 cells produce interleukin-4 (IL-4); however, IL-4 production was not induced by streptococcal H(2)O(2). Furthermore, an in vivo study using the murine pollen-induced allergic rhinitis model suggested that the streptococcal H(2)O(2) reduces nasal allergic reaction. These findings reveal that H(2)O(2) produced by oral mitis group streptococci inhibits IgE-stimulated degranulation by inducing cell death. Consequently, streptococcal H(2)O(2) can be considered to modulate the allergic reaction in mucosal surfaces.