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Mechanisms of impaired neutrophil functions by clinical isolates from bacteremia

Research Project

Project/Area Number 22591116
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Infectious disease medicine
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

ATO Manabu  国立感染症研究所, 免疫部, 室長 (20392318)

Co-Investigator(Renkei-kenkyūsha) OHNISHI Makoto  国立感染症研究所, 細菌第一部, 部長 (10233214)
IKEBE Tadayoshi  国立感染症研究所, 細菌第一部, 主任研究官 (20333362)
KURODA Makoto  国立感染症研究所, 病原体ゲノム解析研究センター, センター長 (80317411)
TOBIUME Minoru  国立感染症研究所, 感染病理部, 主任研究官 (60370962)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords感染症 / 免疫学 / 細菌 / 好中球 / 菌血症 / 免疫回避 / 遺伝子
Research Abstract

Sepsis and disseminated bacterial infection is caused by various bacteria and affected to not only compromised hosts but healthy people without apparent trauma. In this study, we aim to unveil a novel neutrophil-bacteria interaction which regulates host defense by analysis of modification of neutrophil defense functions by screening using human neutrophils and mouse models. Here we show that clinical isolates from severe invasive streptococcus infection have a license to kill neutrophils by streptolysin O, a pore-forming toxin in a contact-depending manner. We demonstrate that clinical isolates from septic melioidosis could suppress the release of neutrophil extracellular traps (NETs), which kill bacteria extracellularly. We further identified bacterial virulence factors responsible to modification of NETs release. These findings are expected to contribute to understanding pathogenesis of invasive bacteria infections.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (39 results)

All 2013 2012 2011 2010 Other

All Journal Article (13 results) (of which Peer Reviewed: 10 results) Presentation (19 results) (of which Invited: 1 results) Book (4 results) Remarks (3 results)

  • [Journal Article] Critical roles for lipomannan and lipoarabinomannan in cell wall integrity of mycobacteria and pathogenesis of tuberculosis.2013

    • Author(s)
      Fukuda T, Matsumura T, Ato M, Hamasaki M, Nishiuchi Y, Murakami Y, Maeda Y, Yoshimori T, Matsumoto S, Kobayashi K, Kinoshita T, Morita Y
    • Journal Title

      mBio

      Volume: 4(1)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 劇症型溶血性レンサ球菌感染症における菌側病原因子と好中球機能傷害の機序2013

    • Author(s)
      阿戸 学、松村隆之、池辺忠義
    • Journal Title

      化学療法の領域 私達の研究(121)

      Volume: 29(4) Pages: 108-117

    • Related Report
      2012 Final Research Report
  • [Journal Article] Critical roles for lipomannan and lipoarabinomannan in cell wall integrity of mycobacteria and pathogenesis of tuberculosis.2013

    • Author(s)
      Fukuda T, Matsumura T, Ato M, Hamasaki M, Nishiuchi Y, Murakami Y, Maeda Y, Yoshimori T, Matsumoto S, Kobayashi K, Kinoshita T, Morita Y.
    • Journal Title

      MBio

      Volume: 4 Issue: 1

    • DOI

      10.1128/mbio.00472-12

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 劇症型溶血性レンサ球菌感染症における菌側病原因子と好中球機能傷害の機序2013

    • Author(s)
      阿戸 学、松村隆之、池辺忠義.
    • Journal Title

      化学療法の領域

      Volume: 29 Pages: 108-117

    • Related Report
      2012 Annual Research Report
  • [Journal Article] 結核及び非定型抗酸菌感染症の診断2012

    • Author(s)
      松村隆之、阿戸 学、小林和夫
    • Journal Title

      リウマチ科 解説

      Volume: 47(4) Pages: 427-435

    • Related Report
      2012 Final Research Report
  • [Journal Article] qNeutrophil extracellular traps exhibit antibacterial activity against Burkholderia pseudomallei and are influenced by bacterial and host factors.2012

    • Author(s)
      Riyapa D, Buddhisa S, Korbsrisate S, Cuccui J, Wren B, Stevens M, Ato M, Lertmemongkolchai G
    • Journal Title

      Infection and Immunity

      Volume: 80(11) Issue: 11 Pages: 3921-9

    • DOI

      10.1128/iai.00806-12

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Brucella abortus exploits a cellular prion protein on intestinal M cells as an invasive receptor.2012

    • Author(s)
      Nakato G, Hase K, Suzuki M, Kimura M, Ato M, Hanazato M, Tobiume M, Horiuchi M, Atarashi R, Nishida N, Watarai M, Imaoka K, Ohno H
    • Journal Title

      Journal of Immunology

      Volume: 189(4) Issue: 4 Pages: 1540-4

    • DOI

      10.4049/jimmunol.1103332

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interferon-γ-producing immature myeloid cells confer protection against severe invasive group A Streptococcus infections2012

    • Author(s)
      Matsumura T, Ato M, Ikebe T, Ohnishi M, Watanabe H, Kazuo Kobayashi
    • Journal Title

      Nat Commun

      Volume: 3 Issue: 1 Pages: 678-678

    • DOI

      10.1038/ncomms1677

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular detection of Anaplasma phagocytophilum in cattle and Ixodes persulcatus ticks2011

    • Author(s)
      Murase Y, Konnai S, Hidano A, Githaka W.N, Ito T, Takano A, Kawabata H, Ato M, Tajima T, Tajima M, Onuma M, Murata S, Ohashi K
    • Journal Title

      Vet.Microbiol.

      Volume: 49 Issue: 3-4 Pages: 504-507

    • DOI

      10.1016/j.vetmic.2010.11.025

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Grobal threads and the control of multi-drug resistant tuberculosis.2011

    • Author(s)
      Kobayashi K, Ato M, Matsumoto S
    • Journal Title

      Journal of Disaster Research

      Volume: 6(4) Pages: 443-450

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular detection of Anaplasma phagocytophilum in cattle and Ixodes persulcatus ticks.2011

    • Author(s)
      Murase Y, Konnai S, Hidano A, Githaka W.N, Ito T, Takano A, Kawabata H, Ato M, Tajima T, Tajima M, Onuma M, Murata S, Ohashi K.
    • Journal Title

      Veterinary Microbiology

      Volume: 印刷中

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Highly frequent mutations in negative regulators of multiple virulence genes in group A streptococcal toxic shock syndrome isolates2010

    • Author(s)
      Ikebe T, Ato M, Matsumura T, Hasegawa H, Sata T, Kobayashi K, Watanabe H
    • Journal Title

      PLoS Pathog

      Volume: 6 Issue: 4 Pages: e1000832-e1000832

    • DOI

      10.1371/journal.ppat.1000832

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Highly frequent mutations in negative regulators of multiple virulence genes in group A streptococcal toxic shock syndrome isolates.2010

    • Author(s)
      Ikebe T, Ato M, Matsumura T, Hasegawa H, Sata T, Kobayashi K, Watanabe H.
    • Journal Title

      PLoS Pathogen

      Volume: 6

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Interferon-gamma-producing immature myeloid cells in severe Streptococcus infection2013

    • Author(s)
      Ato M
    • Organizer
      The Joint international Meeting of The 78th Meeting of the Japanese Society of Interferon and Cytokine Research and The 21st International Symposium on Molecular Cell Biology of Macrophages
    • Place of Presentation
      東京
    • Year and Date
      2013-05-20
    • Related Report
      2012 Final Research Report
  • [Presentation] The defensive role of a novel interferon-γ-producing subpopulation of immature myeloid cells in severe invasive group A Streptococcus infections. 20122013

    • Author(s)
      Matsumura T, Ikebe T, Ohnishi M, Watanabe H, Kobayashi K, Ato M
    • Organizer
      99^<th> Annual meeting The American Society of Immunologists
    • Place of Presentation
      米国 Boston
    • Related Report
      2012 Final Research Report
  • [Presentation] Interferon-gamma-producing immature myeloid cells in severe Streptococcus infection2013

    • Author(s)
      Ato M
    • Organizer
      The Joint international Meeting of The 78th Meeting of the Japanese Society of Interferon and Cytokine Research The 21st International Symposium on Molecular Cell Biology of Macrophages 2013
    • Place of Presentation
      Tokyo
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] The defensive role of a novel interferon-γ-producing subpopulation of immature myeloid cells in severe invasive group A Streptococcus infections.2012

    • Author(s)
      Matsumura T, Ikebe T, Ohnishi M, Watanabe H, Kobayashi K, Ato M.
    • Organizer
      99th Annual meeting The American Society of Immunologists
    • Place of Presentation
      Boston, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] IFN-γ-producing immature myeloid cells confer protection against severe invasive group A Streptococcus infections in mice2011

    • Author(s)
      Matsumura T, Kobayashi K, Ato M
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Year and Date
      2011-11-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] Regulatory genes of multiple virulence factors involved in severe invasive group A streptococcus infection2011

    • Author(s)
      Ato M
    • Organizer
      Singapore-Japan Joint Forum in Emerging Concepts in Microbiology
    • Place of Presentation
      国立シンガポール大学(シンガポール)(招待講演)
    • Year and Date
      2011-11-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Contact with group A Streptococcus isolated from severe invasive infections induces rapid necrosis of human neutrophils2011

    • Author(s)
      Ato M, Ikebe T, Matsumura T, Ohnishi M, Watanabe H, Kobayashi K
    • Organizer
      International Union of Microbiological Societies Congresses 2011
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2011-09-08
    • Related Report
      2011 Annual Research Report
  • [Presentation] 劇症型溶血性レンサ球菌感染症における環状核骨髄系細胞の保護的役割2011

    • Author(s)
      松村隆之、池辺忠義、大西真、渡邉治雄、小林和夫、阿戸学
    • Organizer
      第9回感染症沖縄フォーラム
    • Place of Presentation
      沖縄国民健康センター(沖縄県)
    • Year and Date
      2011-02-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] IFN- -producing immature myeloid cells confer protection against severe invasive group A Streptococcus infections in mice.2011

    • Author(s)
      Matsumura T, Kobayashi K, Ato M
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉市
    • Related Report
      2012 Final Research Report
  • [Presentation] Regulatory genes of multiple virulence factors involved in severe invasive group A streptococcus infection. 20112011

    • Author(s)
      Ato M
    • Organizer
      Singapore-Japan Joint Forum in Emerging Concepts in Microbiology
    • Place of Presentation
      Singapore
    • Related Report
      2012 Final Research Report
  • [Presentation] 2011. Contact with group A Streptococcus isolated from severe invasive infections induces rapid necrosis of human neutrophils.2011

    • Author(s)
      Ato M, Ikebe T, Matsumura T, Ohnishi M, Watanabe H, Kobayashi K.
    • Organizer
      International Union of Microbiological Societies Congresses
    • Place of Presentation
      札幌
    • Related Report
      2012 Final Research Report
  • [Presentation] The protective role of a novel population of IFN-g-producing cells in severe invasive group A streptococcal infections. 2011.2011

    • Author(s)
      Matsumura T, Ikebe T, Ohnishi M, Watanabe H, Kobayashi K, Ato M
    • Organizer
      XVIII Lancefield International Symposium
    • Place of Presentation
      Palermo, Itary
    • Related Report
      2012 Final Research Report
  • [Presentation] novel IFN-g-producing subpopulations of immature myeloid cells confers protection from severe invasive group A Streptococcus infections. 2011.2011

    • Author(s)
      Matsumura T, Ikebe T, Ohnishi M, Watanabe H, Kobayashi K, Ato M
    • Organizer
      19th International Symposium on Molecular Cell Biology of Macrophages
    • Place of Presentation
      泉佐野市
    • Related Report
      2012 Final Research Report
  • [Presentation] Neutrophil dysfunctions by pathogenic bacteria. 2010.2010

    • Author(s)
      Ato M
    • Organizer
      Symposium on High Throughput Approaches in Infection & Immunity
    • Place of Presentation
      Hua Hin, Thailand
    • Year and Date
      2010-12-07
    • Related Report
      2012 Final Research Report
  • [Presentation] Neutrophil dysfunctions by pathogenic bacteria2010

    • Author(s)
      Ato, M.
    • Organizer
      Symposium on High Throughput Approaches in Infection & Immunity
    • Place of Presentation
      Hua Hin, Thailand
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] Identification of IFN-gamma producing cells in severe invasive group A streptococcal infection.2010

    • Author(s)
      Matsumura T., Ikebe T., Watanabe H., Kobayashi K., Ato.
    • Organizer
      14th International Congress of Immunology
    • Place of Presentation
      神戸ポートピアホテル(兵庫県)
    • Year and Date
      2010-08-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] The defensive role of interferon-Y produced by myeloid cells in invasive group A Streptococcus infection.2010

    • Author(s)
      Matsumura T., Ikebe T., Watanabe H., Kobayashi K., Ato.
    • Organizer
      18th International Symposium on Molecular Cell Biology of Macrophages
    • Place of Presentation
      くまもと県民交流館(熊本県)
    • Year and Date
      2010-05-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] Identification of IFN-gamma producing cells in severe invasive group A streptococcal infection. 2010.2010

    • Author(s)
      Matsumura, T., Ikebe T, H. Watanabe, K. Kobayashi, and M. Ato
    • Organizer
      14th International Congress of Immunology
    • Place of Presentation
      神戸
    • Related Report
      2012 Final Research Report
  • [Presentation] The defensive role of interferon-γ produced by myeloid cells in invasive group A Streptococcus infection. 2010.2010

    • Author(s)
      Matsumura, T.. Ikebe T, H. Watanabe, K. Kobayashi, and M. Ato
    • Organizer
      18th International Symposium on Molecular Cell Biology of Macrophages
    • Place of Presentation
      熊本
    • Related Report
      2012 Final Research Report
  • [Book] Myeloid-derived suppressor cells (MDSCs) and their related cell subpopulations. The Research and Biology of Cancer.2012

    • Author(s)
      Matsumura T, Kobayashi K, Ato M
    • Publisher
      iConcept Press
    • Related Report
      2012 Final Research Report
  • [Book] 免疫の事典 阿戸 学 「リケッチア」、大西 真、阿戸 学 「性感染症/性行為感染症」2012

    • Author(s)
      桂 義元、河本 宏、小安重夫、山本一彦 編集
    • Publisher
      朝倉書店
    • Related Report
      2012 Final Research Report
  • [Book] The Research and Biology of Cancer.2012

    • Author(s)
      Matsumura T, Kobayashi K, Ato M.
    • Total Pages
      18
    • Publisher
      iConcept Press
    • Related Report
      2012 Annual Research Report
  • [Book] 免疫の事典2011

    • Author(s)
      桂義元、河本宏、小安重夫、山本一彦編集
    • Total Pages
      473
    • Publisher
      朝倉書店
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.nih.go.jp/niid/ja/from-imm/937-imm-02.html

    • Related Report
      2012 Final Research Report
  • [Remarks] インターフェロンγを産生する未熟骨髄系細胞は劇症型A群レンサ球菌感染に対して防御的に働く

    • URL

      http://www.nih.go.jp/niid/ja/basic-science/iummunology/1717-imm-2012-001.html

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.nih.go.jp/niid/ja/basic-science/iummunology/1717-imm-2012-001.html

    • Related Report
      2011 Annual Research Report

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Published: 2010-11-30   Modified: 2019-07-29  

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