Abstract
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 (H2O2) 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 H2O2, we examined the effect of S. oralis mutant strain deficient in producing H2O2, and found that they lost the ability to suppress the degranulation. Moreover, H2O2 alone inhibited the IgE-induced degranulation. Subsequent analysis suggested that the inhibition of degranulation was related to the cytotoxicity of streptococcal H2O2. Activated RBL-2H3 cells produce interleukin-4 (IL-4); however, IL-4 production was not induced by streptococcal H2O2. Furthermore, an in vivo study using the murine pollen-induced allergic rhinitis model suggested that the streptococcal H2O2 reduces nasal allergic reaction. These findings reveal that H2O2 produced by oral mitis group streptococci inhibits IgE-stimulated degranulation by inducing cell death. Consequently, streptococcal H2O2 can be considered to modulate the allergic reaction in mucosal surfaces.
Highlights
Streptococcus oralis, Streptococcus sanguinis, and Streptococcus gordonii are oral mitis group streptococci, which are the most abundant inhabitants of the oral cavity and dental plaque [1, 2, 3, 4, 5]
Based on the dose-dependency of cytotoxicity, we examined the effects of subcytotoxic doses of S. oralis wild type (WT) (MOI = 1, 2 and 5) and H2O2 (0.01, 0.02, 0.05 mM) on the IgEinduced degranulation (S2 Fig)
We found that sub-cytotoxic doses of S. oralis WT or H2O2 showed no significant effect on Il-4 production from RBL-2H3 cells (S3 Fig)
Summary
Streptococcus oralis, Streptococcus sanguinis, and Streptococcus gordonii are oral mitis group streptococci, which are the most abundant inhabitants of the oral cavity and dental plaque [1, 2, 3, 4, 5] They cause a variety of infectious complications such as bacteremia and infective endocarditis [5, 6, 7, 8, 9]. Mast cells and basophils are key effector cells in immunoglobulin E (IgE)-associated immune response, for example, anaphylaxis and allergic disorders such as allergic rhinitis and pollen-induced allergic rhinitis, that is, pollinosis [15, 16, 17, 18] They have intracellular granules containing allergic mediators (e.g., histamine, serotonin, inflammatory cytokines, proteases and β-hexosaminidase) [15, 16, 18]. The influence of oral bacteria on mast cells in oral tissues and sublingual immunotherapy is unclear
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