PMID- 32302339 OWN - NLM STAT- MEDLINE DCOM- 20200708 LR - 20200708 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 15 IP - 4 DP - 2020 TI - Streptococcal H2O2 inhibits IgE-triggered degranulation of RBL-2H3 mast cell/basophil cell line by inducing cell death. PG - e0231101 LID - 10.1371/journal.pone.0231101 [doi] LID - e0231101 AB - 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 beta-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 beta-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. FAU - Okahashi, Nobuo AU - Okahashi N AUID- ORCID: 0000-0002-8045-7021 AD - Center for Frontier Oral Science, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan. FAU - Nakata, Masanobu AU - Nakata M AD - Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan. FAU - Hirose, Yujiro AU - Hirose Y AD - Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan. FAU - Morisaki, Hirobumi AU - Morisaki H AD - Department of Oral Microbiology and Immunology, School of Dentistry, Showa University, Shinagawa, Tokyo, Japan. FAU - Kataoka, Hideo AU - Kataoka H AD - Department of Oral Microbiology, Asahi University School of Dentistry, Mizuho, Gifu, Japan. FAU - Kuwata, Hirotaka AU - Kuwata H AD - Department of Oral Microbiology and Immunology, School of Dentistry, Showa University, Shinagawa, Tokyo, Japan. FAU - Kawabata, Shigetada AU - Kawabata S AD - Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200417 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Allergens) RN - 0 (Dinitrophenols) RN - 0 (IL4 protein, human) RN - 0 (Plant Extracts) RN - 0 (Sugars) RN - 207137-56-2 (Interleukin-4) RN - 37341-29-0 (Immunoglobulin E) RN - BBX060AN9V (Hydrogen Peroxide) RN - ZIF514RVZR (Serum Albumin, Human) SB - IM MH - Allergens/immunology/*metabolism MH - Animals MH - Basophils/immunology/microbiology/pathology MH - Cell Degranulation/immunology MH - Cell Survival/immunology MH - Dinitrophenols/pharmacology MH - Humans MH - Hydrogen Peroxide/metabolism MH - Hypersensitivity/drug therapy/*immunology/pathology MH - Immunoglobulin E/*immunology/metabolism MH - Interleukin-4/genetics/metabolism MH - Mast Cells/immunology/microbiology/pathology MH - Mice MH - Plant Extracts/chemistry/pharmacology MH - Serum Albumin, Human/immunology/metabolism MH - Streptococcal Infections/*drug therapy/immunology MH - Streptococcus oralis/immunology/pathogenicity MH - Sugars/metabolism PMC - PMC7164662 COIS- The authors have declared that no competing interests exist. EDAT- 2020/04/18 06:00 MHDA- 2020/07/09 06:00 PMCR- 2020/04/17 CRDT- 2020/04/18 06:00 PHST- 2020/01/10 00:00 [received] PHST- 2020/03/16 00:00 [accepted] PHST- 2020/04/18 06:00 [entrez] PHST- 2020/04/18 06:00 [pubmed] PHST- 2020/07/09 06:00 [medline] PHST- 2020/04/17 00:00 [pmc-release] AID - PONE-D-20-00823 [pii] AID - 10.1371/journal.pone.0231101 [doi] PST - epublish SO - PLoS One. 2020 Apr 17;15(4):e0231101. doi: 10.1371/journal.pone.0231101. eCollection 2020.