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Neutrophils in mediastinal lymph node mediates innate immune response during pneumococcal pneumonia.

Research Project

Project/Area Number 17K09659
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNagasaki University

Principal Investigator

YAMAMOTO Kazuko  長崎大学, 病院(医学系), 助教 (10398167)

Co-Investigator(Kenkyū-buntansha) 井手口 周平  長崎大学, 病院(医学系), 医員 (50796224)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords肺炎球菌肺炎 / 縦隔リンパ節 / 好中球 / 侵襲性肺炎球菌感染症 / 自然免疫
Outline of Final Research Achievements

Mediastinal lymph nodes (MLN) are secondary lymphoid organs of the lung. Lymphatic vessels link lung to MLN and MLN to blood. We postulate that innate immune activities in the MLN interrupt bacterial passage, preventing disseminated infection during pneumonia. Our objective was to determine whether neutrophils migrate into MLNs during pneumonia, and to evaluate whether neutrophils in MLN affect bacteremia during pneumonia. Our data showed that neutrophils migrate to MLN during pneumococcal pneumonia, mediated by CXCL1 and CXCL5 in lymphatic endothelial cells, and to prevent bacterial dissemination from the lung via lymphatics. Neutrophils in MLN present MHC class II to stimulate acquired immune response. MLN neutrophils prevent bacteremia during pneumonia.

Academic Significance and Societal Importance of the Research Achievements

肺炎は日本でも死亡者が増加している重要な疾患である。細菌によって引き起こされる肺炎の中で最も頻度が高い肺炎球菌肺炎に対しては、2014年に高齢者に対してワクチン定期接種が導入されたが、いまだ成人の侵襲性肺炎球菌感染症は減少しておらず、予後不良で後遺症もしばしば残る。本研究では、肺炎の動物モデルを用いて、肺の所属リンパ節である縦隔リンパ節で起こる免疫機構について解明したことで、侵襲性肺炎球菌感染症の防御メカニズムの一つが明らかになった。この成果を踏まえて、肺炎の重症化予防に繋がる新たな補助療法の展開に臨みたい。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (24 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (10 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 10 results,  Open Access: 6 results) Presentation (11 results) (of which Int'l Joint Research: 3 results) Book (1 results)

  • [Int'l Joint Research] Boston University School of Medicine(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Boston University School of Medicine(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Epithelial membrane protein 2 governs transepithelial migration of neutrophils into the airspace.2020

    • Author(s)
      Lin WC, Gowdy KM, Madenspacher JH, Zemans RL, Yamamoto K, Lyons-Cohen M, Nakano H, Janardhan K, Williams CJ, Cook DN, Mizgerd JP, Fessler MB.
    • Journal Title

      Journal of Clinical Investigation

      Volume: 130 Issue: 1 Pages: 157-170

    • DOI

      10.1172/jci127144

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A 71-Year-Old Man With Dyspnea and Cough During Chemotherapy2020

    • Author(s)
      Kazuko Yamamoto, Koji Ando, Moe Tanaka, Hirokazu Yura, Noriho Sakamoto, Yoshiaki Zaizen, Kazuto Ashizawa, Junya Fukuoka, Yasushi Miyazaki, Hiroshi Mukae
    • Journal Title

      CHEST

      Volume: 157 Issue: 5 Pages: e165-e171

    • DOI

      10.1016/j.chest.2019.12.008

    • NAID

      120006988201

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and Microbiological Characteristics of Candida guilliermondii and Candida fermentati2018

    • Author(s)
      Hirayama Tatsuro、Miyazaki Taiga、Yamagishi Yuka、Mikamo Hiroshige、et al.
    • Journal Title

      Antimicrobial Agents and Chemotherapy

      Volume: 印刷中 Issue: 6 Pages: 02528-17

    • DOI

      10.1128/aac.02528-17

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] A case of bilateral emphysematous pyelonephritis caused by Candida albicans.2018

    • Author(s)
      Ideguchi S, Yamamoto K, Ikeda A, Hashimoto K, Takazono T, Saijo T, Imamura Y, Miyazaki T, Mukae H.
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 25 Issue: 4 Pages: 302-306

    • DOI

      10.1016/j.jiac.2018.10.011

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regionally compartmentalized resident memory T cells mediate naturally acquired protection against pneumococcal pneumonia.2017

    • Author(s)
      Smith NMS, WassermanGA, Coleman FT, Hilliard KL, Yamamoto K, Lipsitz E, Malley R, Dooms H, Jones MR, Quinton LJ, Mizgerd JP.
    • Journal Title

      Mucosal Immunity

      Volume: 印刷中 Issue: 1 Pages: 220-235

    • DOI

      10.1038/mi.2017.43

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Examination of cryptococcal glucuronoxylomannan antigen in bronchoalveolar lavage fluid for diagnosing pulmonary cryptococcosis in HIV-negative patients2017

    • Author(s)
      Oshima Kazuhiro、Takazono Takahiro、Saijo Tomomi、Tashiro Masato、Kurihara Shintaro、Yamamoto Kazuko、Imamura Yoshifumi、Miyazaki Taiga、Tsukamoto Misuzu、Yanagihara Katsunori、Mukae Hiroshi、Kohno Shigeru、Izumikawa Koichi
    • Journal Title

      Med Mycol

      Volume: 56 Issue: 1 Pages: 88-94

    • DOI

      10.1093/mmy/myx010

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of Piwi protein MIWI2 defines a distinct population of multicilliated cells.2017

    • Author(s)
      Wasserman GA, Szymaniak AD, Hinds AC, Yamamoto K, Kamata H, Smith NMS, Hilliard KL, Carrieri C, Labadorf AT, Quinton LJ, Ai X, Varelas X, Chen F, Mizgerd JP, Fine A, O’Carroll D, Jones MR.
    • Journal Title

      Journal of Clinical Investigation

      Volume: 127 Issue: 10 Pages: 3866-3876

    • DOI

      10.1172/jci94639

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The capacity of pneumococci to activate macrophage NF-kB determines necroptosis and pneumonia severity.2017

    • Author(s)
      Coleman FT, Blahna MT, Kamata H, Yamamoto K, Zabinski MC, Kramnik I, Wilson AA, Kotton DN, Quinton LJ, Jones MR, Pelton SI, Mizgerd JP
    • Journal Title

      Journal of Infectious Diseases

      Volume: 216 Issue: 4 Pages: 425-435

    • DOI

      10.1093/infdis/jix159

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In vitro and In vivo antifungal activities of T-2307, a novel arylamidine, against Cryptococcus gatiii: an emerging fungal pathogen.2017

    • Author(s)
      Nishikawa H, Fukuda Y, Mitsuyama J, Tashiro M, Tanaka A, Takazono T, Saijo T, Yamamoto K, Nakamura S, Imamura Y, Miyazaki T, Kakeya H, Yamamoto Y, Yanagihara K, Mukae H, Kohno S, Izumikawa K.
    • Journal Title

      Journal of Antimicrobial Chemotherapy

      Volume: 72 Issue: 6 Pages: 1709-1713

    • DOI

      10.1093/jac/dkx020

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparison of Efficacy of Antimicrobial Agents Among Hospitalized Patients With Mycoplasma pneumoniae Pneumonia in Japan During Large Epidemics of Macrolide-Resistant M. pneumoniae Infections: A Nationwide Observational Study2017

    • Author(s)
      Tashiro Masato、Fushimi Kiyohide、Kawano Kei、Takazono Takahiro、Saijo Tomomi、Yamamoto Kazuko、Kurihara Shintaro、Imamura Yoshifumi、Miyazaki Taiga、Yanagihara Katsunori、Mukae Hiroshi、Izumikawa Koichi
    • Journal Title

      Clin Infect Dis

      Volume: 65 Issue: 11 Pages: 1837-1842

    • DOI

      10.1093/cid/cix695

    • NAID

      120006988062

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 肺炎球菌株のマクロファージ NF-kB活性誘導能がもつ臨床的な意義2019

    • Author(s)
      井手口周平、山本和子、高園貴弘、西條知見、今村圭文、宮崎泰可、柳原克紀、福田雄一、一門和哉、小宮幸作、門田淳一、矢寺和博、常 彬、迎 寛
    • Organizer
      第59回日本呼吸器学会学術講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The capacity of pneumococcus to stimulate macrophage NF-kappa B activity dictates the seveerity of adult pneumococcal pneumonia2018

    • Author(s)
      Kazuko Yamamoto, Shuhei Ideguchi, Shotaro Ide, Takahiro Takazono, Tomomi Saijo, Yoshifumi Imamura, Taiga Miyazaki, Katsunori Yanagihara, Yuichi Fukuda, Bin Chang, Fadie T. Coleman, Joseph P. Mizgerd, Hiroshi Mukae
    • Organizer
      Gordon Research Conference 2018, Biology of Acute Respiratory Infection
    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] The impact of neutrophil recruitment in mediastinal lymph node to invasive pneumococcal pneumonia2018

    • Author(s)
      Kazuko Yamamoto
    • Organizer
      第58回日本呼吸器学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肺炎球菌のマクロファージ NF-kB活性誘導能と肺炎の臨床像との関連性2018

    • Author(s)
      井手口周平、山本和子、鍵本啓介、井手昇太郎、高園貴弘、西條知見、今村圭文、宮崎泰可、柳原克紀、福田雄一、常彬、迎寛
    • Organizer
      第58回日本呼吸器学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] The capacity of pneumococcus to stimulate macrophage NF-kappa B activity dictates the seveerity of adult pneumococcal pneumonia2018

    • Author(s)
      Shuhei Ideguchi, Kazuko Yamamoto, Shotaro Ide, Takahiro Takazono, Tomomi Saijo, Yoshifumi Imamura, Taiga Miyazaki, Katsunori Yanagihara, Yuichi Fukuda, Shigeki Nakamura, Bin Chang, Fadie T. Coleman, Joseph P. Mizgerd, Hiroshi Mukae
    • Organizer
      American Thoracic Society (ATS) 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 肺炎球菌肺炎における肺自然免疫機構2018

    • Author(s)
      山本和子
    • Organizer
      第46回箱根呼吸討論会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肺炎の免疫治療の可能性. 肺炎球菌肺炎の免疫応答を参考に.2018

    • Author(s)
      山本和子
    • Organizer
      第81回日本呼吸器学会 秋季九州地方会
    • Related Report
      2018 Research-status Report
  • [Presentation] The impact of neutrophil recruitment in mediastinal lymph node to invasive pneumococcal pneumonia2018

    • Author(s)
      山本 和子
    • Organizer
      第58回日本呼吸器学会学術講演会
    • Related Report
      2017 Research-status Report
  • [Presentation] 縦隔リンパ節内好中球による肺炎球菌肺炎の侵襲性感染症の防御2017

    • Author(s)
      山本 和子, 田中 章貴, 田代 将人, 西條 知見, 今村 圭文, 宮崎 泰可, 泉川 公一, 迎 寛
    • Organizer
      第57回日本呼吸器学会学術講演会
    • Related Report
      2017 Research-status Report
  • [Presentation] 当科における膿胸の治療経過に関連する患者背景因子の検討2017

    • Author(s)
      井手口 周平, 山本 和子, 井手 昇太郎, 田中 章貴, 田代 将人, 小佐井 康介, 賀来 敬仁, 西條 知見, 今村 圭文, 宮崎 泰可, 泉川 公一, 柳原 克紀, 迎 寛
    • Organizer
      第91回日本感染症学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Significance of antimicrobial treatment-related factors for the outcomes of adult empyema in Japanese tertiary hospitals2017

    • Author(s)
      Daisuke Okuno, Shuhei Ideguchi, Kazuko Yamamoto, Tomomi Saijo, Yoshifumi Imamura, Taiga Miyazaki, Naoki Iwanaga, Yuichi Fukuda, Kazuhiro Yatera, Hiroshi Mukae
    • Organizer
      30th International Congress of Chemotherapy and Infection 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] Pulmonary Disease Series: Clinical relevance of genetic factors in pulmonary diseases.2018

    • Author(s)
      Yamamoto K, Mukae H.
    • Total Pages
      344
    • Publisher
      Springer
    • ISBN
      9789811081439
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2022-02-21  

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