Infection by oral mitis group streptococci induces impairment of mast cell function and allergic response

• Project/Area Number: 17K11958
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Osaka University
• Principal Investigator: Okahashi Nobuo 大阪大学, 歯学研究科, 准教授 (40150180)
• Co-Investigator(Kenkyū-buntansha): 中田 匡宣 鹿児島大学, 医歯学域歯学系, 教授 (90444497)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 口腔レンサ球菌 / マスト細胞 / アレルギー / 細胞死 / 過酸化水素

Outline of Final Research Achievements

Mast cells play central roles in allergic reaction. In this study, we found that H2O2 produced by mitis group streptococci such as Streptococcus oralis reduced degranulation of mast cells stimulated with IgE-antigen complex. The reduction of the degranulation was related to the H2O2-induced cell death. Lysosomal dysfunction by H2O2 seemed to contribute to the unique cell death. Using mouse model of pollen allergy, we found that streptococcus-derived H2O2 reduced the sneezing of the sensitized mice challenged with cedar pollen. These results suggest that H2O2 produced by the oral mitis group streptococci is able to disrupt the host allergic reaction.

Academic Significance and Societal Importance of the Research Achievements

口腔ミティス群レンサ球菌が産生する低濃度の過酸化水素が宿主の免疫応答やアレルギー応答に影響を与える可能性が示された．口腔常在細菌の代謝産物にそのような作用があることは従来全く想定されておらず、常在細菌が宿主に与える影響を考え直す必要があるのではないかと思われる．

Research Products

• [Journal Article] Streptococcus pyogenes upregulates arginine catabolism to exert its pathogenesis on the skin surface (2021)
  • Author(s): Hirose Yujiro、Yamaguchi Masaya、Sumitomo Tomoko、Nakata Masanobu、Hanada Tomoki、Okuzaki Daisuke、Motooka Daisuke、Mori Yasushi、Kawasaki Hiroshi、Coady Alison、Uchiyama Satoshi、Hiraoka Masanobu、Zurich Raymond H.、Amagai Masayuki、Nizet Victor、Kawabata Shigetada
  • Journal Title: Cell Reports Volume: 34 Issue: 13 Pages: 108924-108924
  • DOI: 10.1016/j.celrep.2021.108924
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Streptococcal H2O2 Inhibits IgE-triggered Degranulation of RBL-2H3 Mast Cell/Basophil Cell Line by Inducing Cell Death (2020)
  • Author(s): Okahashi N, Nakata M, Hirose Y, Morisaki H, Kataoka H, Kuwata H, KawabataS.
  • Journal Title: PLoS One Volume: 15 Issue: 4 Pages: e0231101-e0231101
  • DOI: 10.1371/journal.pone.0231101
  • Peer Reviewed / Open Access
• [Journal Article] Role of BgaA as a pneumococcal virulence factor elucidated by molecular evolutionary analysis. (2020)
  • Author(s): Yamaguchi M, Takemura M, Higashi K, Goto K, Hirose Y, Sumitomo T, Nakata M, Uzawa N, Kawabata S.
  • Journal Title: Front Microbiol Volume: 11 Pages: 582437-582437
  • DOI: 10.3389/fmicb.2020.582437
  • Peer Reviewed / Open Access
• [Journal Article] Detection of fibronectin-binding proteins of Streptococcus pyogenes using ligand blot analysis (2020)
  • Author(s): Nakata M, Kawabata S.
  • Journal Title: Methods Mol Biol Volume: 113(1) Pages: 181-190
  • DOI: 10.1007/978-1-0716-0467-0_13
  • ISBN: 9781071604663, 9781071604670
  • Peer Reviewed / Open Access
• [Journal Article] Thermosensitive pilus production by FCT type 3 Streptococcus pyogenes controlled by Nra regulator translational efficiency. (2020)
  • Author(s): Nakata M, Sumitomo T, Patenge N, Kreikemeyer B, Kawabata S.
  • Journal Title: Mol Microbiol Volume: 113 Issue: 1 Pages: 173-189
  • DOI: 10.1111/mmi.14408
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dysregulation of Intestinal Microbiota Elicited by Food Allergy Induces IgA-Mediated Oral Dysbiosis (2019)
  • Author(s): Matsui Shohei、Kataoka Hideo、Tanaka Jun-Ichi、Kikuchi Mariko、Fukamachi Haruka、Morisaki Hirobumi、Matsushima Hitomi、Mishima Kenji、Hironaka Shoji、Takaki Takashi、Okahashi Nobuo、Maruoka Yasubumi、Kuwata Hirotaka
  • Journal Title: Infection and Immunity Volume: 88 Issue: 1
  • DOI: 10.1128/iai.00741-19
  • Peer Reviewed / Open Access
• [Journal Article] Streptococcus pneumoniae evades host cell phagocytosis and limits host mortality through its cell wall anchoring protein PfbA. (2019)
  • Author(s): Yamaguchi M, Hirose Y, Takemura M, Ono M, Sumitomo T, Nakata M, Terao Y, Kawabata S.
  • Journal Title: Front Cell Infect Microbiol Volume: 9 Pages: 301-301
  • DOI: 10.3389/fcimb.2019.00301
  • Peer Reviewed / Open Access
• [Journal Article] Streptococcus pyogenes transcriptome changes in the inflammatory environment of necrotizing fasciitis. (2019)
  • Author(s): Hirose Y, Yamaguchi M, Okuzaki D, Motooka D, Hamamoto H, Hanada T, Sumitomo T, Nakata M, Kawabata S.
  • Journal Title: Appl Environ Microbiol Volume: 85 Issue: 21
  • DOI: 10.1128/aem.01428-19
  • Peer Reviewed / Open Access
• [Journal Article] Allergic conversion of protective mucosal immunity against nasal bacteria in patients with chronic rhinosinusitis with nasal polyposis. (2019)
  • Author(s): Takeda K, Sakakibara S, Yamashita K, Motooka D, Nakamura S, El Hussien MA, Katayama J, Maeda Y, Nakata M, Hamada S, Standley DM, Hayama M, Shikina T, Inohara H, Kikutani H.
  • Journal Title: J Allergy Clin Immunol Volume: 143 Issue: 3 Pages: 1163-1175
  • DOI: 10.1016/j.jaci.2018.07.006
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of evolutionarily conserved virulence factor by selective pressure analysis of Streptococcus pneumoniae (2019)
  • Author(s): Yamaguchi M, Goto K, Hirose Y, Yamaguchi Y, Sumitomo T, Nakata M, Nakano K, Kawabata S.
  • Journal Title: Commun Biol Volume: 2 Issue: 1 Pages: 96-96
  • DOI: 10.1038/s42003-019-0340-7
  • Peer Reviewed / Open Access
• [Journal Article] Competence-induced protein Ccs4 facilitates pneumococcal invasion into brain tissue and virulence in meningitis. (2018)
  • Author(s): Hirose Y, Yamaguchi M, Goto K, Sumitomo T, Nakata M, Kawabata S.
  • Journal Title: Virulence Volume: 9 Issue: 1 Pages: 1576-1587
  • DOI: 10.1080/21505594.2018.1526530
  • Peer Reviewed / Open Access
• [Journal Article] Streptococcus sanguinis non-coding csRNAs negatively regulate expression of type IV pilus retraction ATPase PilT and biofilm formation (2018)
  • Author(s): Ota C, Morisaki H, Nakata M, Arimoto T, Fukamachi H, Kataoka H, Masuda Y, Suzuki N, Miyazaki T, Okahashi N, Kuwata H
  • Journal Title: Infect Immun Volume: 86 Issue: 3 Pages: 1-13
  • DOI: 10.1128/iai.00894-17
  • Peer Reviewed / Open Access
• [Journal Article] Streptococcal Cysteine Protease-Mediated Cleavage of Desmogleins Is Involved in the Pathogenesis of Cutaneous Infection (2018)
  • Author(s): Sumitomo Tomoko、Mori Yasushi、Nakamura Yuumi、Honda-Ogawa Mariko、Nakagawa Seitaro、Yamaguchi Masaya、Matsue Hiroyuki、Terao Yutaka、Nakata Masanobu、Kawabata Shigetada
  • Journal Title: Front Cell Infect Microbiol Volume: 8 Pages: 10-10
  • DOI: 10.3389/fcimb.2018.00010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Microarray analysis of macrophage response to infection with Streptococcus oralis reveals the immunosuppressive effect of hydrogen peroxide (2017)
  • Author(s): H. Matsushima, Y. Kumagai, A. Vandenbon, H. Kataoka, M. Kadena, H. Fukamachi, T. Arimoto, H. Morisaki, N. Fujiwara, N. Okahashi, and H. Kuwata
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 485(2) Issue: 2 Pages: 461-467
  • DOI: 10.1016/j.bbrc.2017.02.048
  • Peer Reviewed / Open Access
• [Journal Article] Streptococcus gallolyticus subsp. gallolyticus endocarditis isolate interferes with coagulation and activates the contact system (2017)
  • Author(s): Isenring Julia、Kohler Juliane、Nakata Masanobu、Frank Marcus、Jans Christoph、Renault Pierre、Danne Camille、Dramsi Shaynoor、Kreikemeyer Bernd、Oehmcke-Hecht Sonja
  • Journal Title: Virulence Volume: 9 Issue: 1 Pages: 248-261
  • DOI: 10.1080/21505594.2017.1393600
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Zinc metalloproteinase ZmpC suppresses experimental pneumococcal meningitis by inhibiting bacterial invasion of central nervous systems (2017)
  • Author(s): Yamaguchi Masaya、Nakata Masanobu、Sumioka Ryuichi、Hirose Yujiro、Wada Satoshi、Akeda Yukihiro、Sumitomo Tomoko、Kawabata Shigetada
  • Journal Title: Virulence Volume: 8 Issue: 8 Pages: 1516-1524
  • DOI: 10.1080/21505594.2017.1328333
  • Peer Reviewed / Open Access
• [Presentation] 鼻咽腔に定着する肺炎球菌が非血行性に脳へ伝播する機構の解析． (2021)
  • Author(s): 高原悠樹，住友倫子，河野正充，山口雅也，中田匡宣，保富宗城，川端重忠
  • Organizer: 第94回日本細菌学会総会
• [Presentation] 化膿レンサ球菌におけるヒアルロン酸分解酵素の分子系統解析およびタンパク質結晶構造解析 (2020)
  • Author(s): 東孝太郎，山口雅也，中田匡宣，武部克希，住友倫子，鈴木守，川端重忠
  • Organizer: 第43回日本分子生物学会年会
• [Presentation] Conserved mutation in transcriptional regulator nra gene influences serotype M18 Streptococcus pyogenes virulence-associated phenotypes. (2020)
  • Author(s): Nakata M, Li Y, Sumitomo T, Hirose Y, Takemura M, Yamaguchi M, Okahashi N, Kawabata S
  • Organizer: ASM Microbe 2020
  • Int'l Joint Research
• [Presentation] 血清型M49型 Streptococcus pyogenes のCvfAは病原因子の発現と温度依存性の線毛産生に関与する (2020)
  • Author(s): 窪田星子，中田匡宣，広瀬雄二郎，山口雅也，住友倫子，川端重忠
  • Organizer: 第62回歯科基礎医学会学術大会
• [Presentation] 化膿レンサ球菌による温度依存性の線毛産生 (2020)
  • Author(s): 中田匡宣，住友倫子，川端重忠.
  • Organizer: 第93回 日本細菌学会総会
• [Presentation] Component analysis of cell-wall anchored pili in Streptococcus sanguinis. (2019)
  • Author(s): 李怡萱，中田匡宣，岡橋暢夫，山口雅也，住友倫子，川端重忠.
  • Organizer: 第92回 日本細菌学会総会
• [Presentation] Intestinal dysbiosis elicited by excessive Th2 responses induces oral dysbiosis (2019)
  • Author(s): 松井庄平、片岡嗣雄、深町はるか、森崎弘史、岡橋暢夫、桑田啓貴
  • Organizer: 第92回 日本細菌学会総会
• [Presentation] Two-component regulatory system TCS08 contributes to pathogenesis in pneumococcal pneumonia． (2019)
  • Author(s): Sumitomo T，Hamd DT，Honda-Ogawa M，Mori Y，Yamaguchi M，Nakata M，Kawabata S．
  • Organizer: ASM Microbe 2019
  • Int'l Joint Research
• [Presentation] 日本における劇症型感染症由来 Streptococcus pyogenes emm 89型の解析 (2019)
  • Author(s): 広瀬雄二郎，山口雅也，奥野ルミ，秋山徹，菅原庸，浜田茂幸，住友倫子，中田匡宣，川端重忠
  • Organizer: 第51回 レンサ球菌研究会
• [Presentation] Identification of novel pneumococcal virulence factor CbpJ by molecular evolutional analysis. (2018)
  • Author(s): Yamaguchi M, Goto K, Hirose Y, Yamaguchi Y, Sumitomo T, Nakata M, Kawabata S.
  • Organizer: Gordon Research Conference
  • Int'l Joint Research
• [Presentation] ミティス群レンサ球菌が産生する過酸化水素はマスト細胞の細胞死を誘導し，脱顆粒を抑制する (2018)
  • Author(s): 岡橋暢夫, 中田匡宣, 広瀬雄二郎, 桑田啓貴, 川端重忠
  • Organizer: 第60回歯科基礎医学会学術大会
• [Presentation] Component analysis of cell-wall anchored pili of Streptococcus sanguinis (2018)
  • Author(s): 李怡萱, 中田匡宣, 岡橋暢夫, 山口雅也, 住友倫子, 川端重忠
  • Organizer: 第60回歯科基礎医学会学術大会
• [Presentation] 化膿レンサ球菌のアルギニンデイミナーゼArcAは低グルコース環境下で病原因子の発現に寄与する (2018)
  • Author(s): 広瀬雄二郎， 山口雅也， 毛利泰士， 後藤花奈， 住友倫子， 中田匡宣， 川端重忠
  • Organizer: 第60回歯科基礎医学会学術大会
• [Presentation] インフルエンザウイルスとStreptococcus sanguinis の共感染による肺炎発症メカニズムの解析 (2018)
  • Author(s): 長瀬賢史、住友倫子、中田匡宣、川端重忠、岡本成史
  • Organizer: 第50回レンサ球菌研究会
• [Presentation] Streptococcus pneumoniae evades host innate immunity through parallel β-helix protein PfbA. (2017)
  • Author(s): Yamaguchi M, Hirose Y, Goto K, Sumitomo T, Nakata M, Kawabata S.
  • Organizer: 20th Lancefield International Symposium on Streptococci and Streptococal Disease
  • Int'l Joint Research
• [Presentation] Streptococcal cysteine protease-mediated cleavage of desmogleins contributes to development of cutaneous infection. (2017)
  • Author(s): Sumitomo T, Mori Y, Nakamura Y, Honda-Ogawa M, Yamaguchi M, Terao Y, Nakata M, and Kawabata S.
  • Organizer: IUMS2017
  • Int'l Joint Research
• [Presentation] Streptococcus pneumoniae Ccs4 は脳血管内皮細胞への付着・侵入を促進する病原因子である (2017)
  • Author(s): 広瀬雄二郎，山口雅也，後藤花奈，住友倫子，中田匡宣，川端重忠
  • Organizer: 第40回日本分子生物学会
• [Presentation] 化膿レンサ球菌における温度感受性の線毛発現機構 (2017)
  • Author(s): 中田匡宣，住友倫子，川端重忠
  • Organizer: 第59回歯科基礎医学会学術大会