• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Functional analysis of immature myeloid cells in severe invasive group A streptococcal infection

Research Project

Project/Area Number 16K09952
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Infectious disease medicine
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Matsumura Takayuki  国立感染症研究所, 免疫部, 主任研究官 (50434379)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords免疫学 / 細菌感染症 / 感染症防御学 / 劇症型溶血性レンサ球菌感染症
Outline of Final Research Achievements

Severe invasive group A Streptococcus (GAS) infection evades anti-bacterial immunity by attenuating the cellular components of innate immune responses. However, this loss of protection is compensated for by IFN-γ-producing immature myeloid cells (γIMCs). Here, we demonstrate that γIMCs provide this IFN-γ-mediated protection by sequentially sensing GAS through two distinct pattern recognition receptors. GAS is initially recognized by TLR2, which promptly induces IL-6 production in γIMCs. γIMC-derived IL-6 promotes the upregulation of a recently identified GAS-sensing receptor, macrophage-inducible C-type lectin (Mincle), in an autocrine or paracrine manner. Notably, blockade of γIMC-derived IL-6 abrogates Mincle expression, downstream IFN-γ production, and γIMC-mediated protection against severe invasive GAS infection. Thus, γIMCs regulate host protective immunity against severe invasive GAS infection via a TLR2-IL-6-Mincle axis.

Academic Significance and Societal Importance of the Research Achievements

劇症型溶血性レンサ球菌感染症は約30%が死亡する致死率の高い感染症であり、メディア等では「人食いバクテリア」と称されている。国内年間報告数は、1999~2010年では多くても100例前後で推移、2011~2013年では200例前後を推移していたが、2014年に260例を超えてから増加の一途をたどり、2018年では680例を超えた。したがって既存の抗生物質による治療に追加可能な新規治療法の開発が必要であると考えられる。本研究の成果は、劇症型感染マウスモデルにおいて、新規細胞による連続的なレンサ球菌の認識機構が感染をコントロールできる可能性を見出している。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (13 results)

All 2019 2018 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (9 results) (of which Invited: 1 results)

  • [Journal Article] Streptococcal toxic shock syndrome caused by β-hemolytic streptococci: clinical features and cytokine and chemokine analyses of 15 cases.2019

    • Author(s)
      Yoshizawa S, Matsumura T, Ikebe T, Ichibayashi R, Fukui Y, Satoh T, Tsubota T, Honda M, Ishii Y, Tateda K, Ato M.
    • Journal Title

      J Infect Chemother

      Volume: 25 Issue: 5 Pages: 355-361

    • DOI

      10.1016/j.jiac.2019.01.006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sequential Sensing by TLR2 and Mincle Directs Immature Myeloid Cells to Protect against Invasive Group A Streptococcal Infection in Mice2019

    • Author(s)
      Matsumura Takayuki、Ikebe Tadayoshi、Arikawa Koji、Hosokawa Masahito、Aiko Michio、Iguchi Aoi、Togashi Ikuko、Kai Sayaka、Ohara Sakiko、Ohara Naoya、Ohnishi Makoto、Watanabe Haruo、Kobayashi Kazuo、Takeyama Haruko、Yamasaki Sho、Takahashi Yoshimasa、Ato Manabu
    • Journal Title

      Cell Reports

      Volume: 27 Issue: 2 Pages: 561-571

    • DOI

      10.1016/j.celrep.2019.03.056

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lipoteichoic acid anchor triggers Mincle to drive protective immunity against invasive group AStreptococcusinfection2018

    • Author(s)
      Imai Takashi、Matsumura Takayuki、Mayer-Lambertz Sabine、Wells Christine A.、Ishikawa Eri、Butcher Suzanne K.、Barnett Timothy C.、Walker Mark J.、Imamura Akihiro、Ishida Hideharu、Ikebe Tadayoshi、Miyamoto Tomofumi、Ato Manabu、Ohga Shouichi、Lepenies Bernd、van Sorge Nina M.、Yamasaki Sho
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 115 Issue: 45

    • DOI

      10.1073/pnas.1809100115

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Spontaneous mutations in Streptococcus pyogenes isolates from streptococcal toxic shock syndrome patients play roles in virulence.2016

    • Author(s)
      1.Ikebe T, Matsumura T, Nihonmatsu H, Ohya H, Okuno R, Mitsui C, Kawahara R, Kameyama M, Sasaki M, Shimada N, Ato M, Ohnishi M.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 28761-28761

    • DOI

      10.1038/srep28761

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Group A Streptococcus regulates host immune responses activated via Mincle by changing its lipoteichoic acid anchor2019

    • Author(s)
      Takashi Imai, Takayuki Matsumura, Manabu Ato, Tomofumi Miyamoto, Sho Yamasaki, Shouichi Ohga
    • Organizer
      第93回日本感染症学会総会・学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The TLR2-L-6-Mincle axis is essential to protect against severe invasive streptococcal infection2019

    • Author(s)
      Takayuki Matsumura, Tadayoshi Ikebe, Makoto Ohnishi, Sho Yamasaki, Yoshimasa Takahashi, Manabu Ato
    • Organizer
      第92回日本細菌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A群レンサ球菌感染制御における未熟骨髄系細胞の役割2018

    • Author(s)
      松村隆之
    • Organizer
      第17回微生物研究会「微生物分子生物学のフロンティア」
    • Related Report
      2018 Annual Research Report
  • [Presentation] Critical role of Mincle in protection against invasive infection by group A Streptococcus2018

    • Author(s)
      Takashi Imai, Takayuki Matsumura, Tomofumi Miyamoto, Manabu Ato, Sho Yamasaki, Shouichi Ohga
    • Organizer
      第50回日本小児感染症学会総会・学術集会/第9回アジア小児感染症学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The IL-6/Mincle axis in immature myeloid cells is critical to protect against severe invasive group A Streptococcus infection2018

    • Author(s)
      Takayuki Matsumura, Sho Yamasaki, Manabu Ato, Yoshimasa Takahashi
    • Organizer
      第47回日本免疫学会総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] IL-6-deficient immature myeloid cells have no protective function against Streptococcus infection2017

    • Author(s)
      Takayuki Matsumura, Tadayoshi Ikebe, Makoto Ohnishi, and Manabu Ato
    • Organizer
      第90回日本細菌学会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-19
    • Related Report
      2016 Research-status Report
  • [Presentation] 劇症型溶血性レンサ球菌感染症における未熟骨髄系細胞の機能解析2017

    • Author(s)
      松村隆之、池辺忠義、大西真、阿戸学
    • Organizer
      第100回日本細菌学会関東支部会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Balance of pro- and anti-inflammatory cytokines in immature myeloid cells involved in outcome of severe invasive group A Streptococcus infections2017

    • Author(s)
      Takayuki Matsumura, Manabu Ato
    • Organizer
      第46回日本免疫学会
    • Related Report
      2017 Research-status Report
  • [Presentation] IL-6-deficient immature myeloid cells do not contribute to an effective host defense during severe invasive group A streptococcal infections2016

    • Author(s)
      Takayuki Matsumura and Manabu Ato
    • Organizer
      第45回日本免疫学会
    • Place of Presentation
      沖縄
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi