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

Analysis of multiple defense mechanisms of "type 3 immune response" in mycobacteria infected lungs

Research Project

Project/Area Number 18K07117
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49050:Bacteriology-related
Research InstitutionUniversity of the Ryukyus

Principal Investigator

Umemura Masayuki  琉球大学, 熱帯生物圏研究センター, 准教授 (90359985)

Co-Investigator(Kenkyū-buntansha) 松崎 吾朗  琉球大学, 熱帯生物圏研究センター, 教授 (30229455)
高江洲 義一  琉球大学, 熱帯生物圏研究センター, 准教授 (60403995)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsinterleukin-17 / TCR γδ T細胞 / 結核 / 肺 / interleukin-1β / interleukin-23 / 結核菌 / TcR γδT細胞 / IL-17 / 3型免疫応答 / IL-23 / IL-1β / IL-17A / γδ T細胞 / 肉芽腫
Outline of Final Research Achievements

We examined which mechanisms of γδ T cells induce mycobacteria antigen (PPD)-specific IL-17A production. In transwell culture with γδ T cells and antigen presenting cells (APC) plus PPD, IL-17A-producing γδ T (γδT17) cells showed increased IL-17A production, and similar results were obtained in experiments with APCs derived from IL-23p19 KO mice. When IL-1β and IL-23 were neutralized, the enhancement of IL-17A production was remarkably reduced. When PPD was directly added to the infected lymphocytes without APC, IL-17A production of γδT17 cells increased. These results suggest that the IL-1β but not IL-23 is essential in IL-17A production by γδT17 cells. On the contrary, enhancement of γδT17 cells was also observed in a system in which PPD stimulation was directly applied to lung lymphocytes. This suggests that suggest that recognition of PPD by T cell receptor or pattern recognition receptors is also important in IL-17A production of γδT17 cells.

Academic Significance and Societal Importance of the Research Achievements

医学ならびに医療技術の発展により不治の病とされてきた結核も人為的制御可能な疾患になりつつある。しかし、現在唯一実用化されている結核ワクチンであるBCGは、小児結核の発病予防には高い効果が認められているものの、成人に対しての予防効果は極めて低い。また、結核菌は結核菌特異的な獲得免疫応答の誘導を何らかの機序で遅延させるが、その現象はBCGを接種しても回避できない。本研究で得られた成果はこれまでのIFN-γ産生を主体とした細胞性免疫を増強させるというワクチン開発のドグマから脱け出す新たな発想を生むための非常に重要な基盤研究である。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (41 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (35 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results) Remarks (2 results)

  • [Journal Article] GRIM-19 is a target of mycobacterial Zn2+ metalloprotease 1 and indispensable for NLRP3 inflammasome activation.2022

    • Author(s)
      Kurane, T., Matsunaga, T., Ida, T., Sawada, K., Nishimura, A., Fukui, M., Umemura, M., Nakayama, M., Ohara, N., Matsumoto, S., Akaike, T., Matsuzaki, G., Takaesu, G.
    • Journal Title

      FASEB Journal

      Volume: 36 Issue: 1

    • DOI

      10.1096/fj.202101074rr

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation.2021

    • Author(s)
      Iizasa, E., Chuma, Y., Uematsu, T., Kubota, M., Kawaguchi, H., Umemura, M., Toyonaga, K., Kiyohara, H., Yano, I., Colonna, M., Sugita, M., Matsuzaki, G., Yamasaki, S., Yoshida, H., Hara, H.
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 2299-2314

    • DOI

      10.1038/s41467-021-22620-3

    • NAID

      120007170570

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Porphyromonas gingivalis components/secretions synergistically enhance pneumonia caused by Streptococcus pneumoniae in mice.2021

    • Author(s)
      Okabe, T., Kamiya, Y., Kikuchi, T., Goto, H., Umemura, M., Suzuki, Y., Sugita, Y., Naiki, Y., Hasegawa, Y., Hayashi, J., Kawamura, S., Sawada, N., Takayanagi, Y., Fujimura, T., Higuchi, N., Mitani, A.
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 22 Issue: 23 Pages: 12704-12715

    • DOI

      10.3390/ijms222312704

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dispensable role of chemokine receptors in migration of mycobacterial antigen-specific CD4+ T cells into Mycobacterium-infected lung2019

    • Author(s)
      Matsuzaki Goro、Yamasaki Masatoshi、Tamura Toshiki、Umemura Masayuki
    • Journal Title

      Immunobiology

      Volume: S0171-2985 Issue: 3 Pages: 30008-7

    • DOI

      10.1016/j.imbio.2019.01.006

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] P. gingivalis components/secretions synergistically enhance pneumonia caused by S. pneumoniae2022

    • Author(s)
      Teppei Okabe, Yosuke Kamiya, Takeshi Kikuchi, Masayuki Umemura, Yoshihiko Sugita, Yoshikazu Naiki, Yoshiaki Hasegawa, Jun-ichiro Hayashi, Naoya Higuchi, Akio Mitani
    • Organizer
      第95回日本細菌学会総
    • Related Report
      2021 Annual Research Report
  • [Presentation] Analysis of Card9 function in pulmonary mycobacterial infection2022

    • Author(s)
      Kenji Toyonaga, Masayuki Umemura, Goro Matsuzaki, Hiromitsu Hara, Yoshihiko Tanaka, and Sho Yamasaki
    • Organizer
      第95回日本細菌学会総
    • Related Report
      2021 Annual Research Report
  • [Presentation] TREM2は非糖鎖付加ミコール酸を認識し、マクロファージの抗抗酸菌免疫応答を抑制する2021

    • Author(s)
      飯笹英一, 中馬康志, 植松崇之, 久保田未央, 川口博明, 梅村正幸, 豊永憲司, 清原秀泰, 矢野郁也, Marco Colonna, 杉田昌彦, 松崎吾朗, 山崎晶, 吉田裕樹, 原博満
    • Organizer
      第85回日本インターフェロン・サイトカイン学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 結核菌由来病原因子Zmp1欠損の感染防御への影響2021

    • Author(s)
      梅村正幸, 松本壮吉, 藏根友美, 高江洲義一, 松﨑吾朗
    • Organizer
      第32回日本生体防御学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 結核菌エフェクタータンパク質によるIL-1β産生阻害の分子機序2021

    • Author(s)
      藏根友美, 高江洲義一, 松永哲郎, 井田 智章, 澤田和子, 梅村正幸, 赤池孝章, 松﨑吾朗
    • Organizer
      第32回日本生体防御学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 結核菌のエフェクタータンパク質Zmp1と会合する宿主E3ユビキチンリガーゼの機能解析2021

    • Author(s)
      高江洲義一, Nguen Huong Minh, 梅村正幸, 松﨑吾朗
    • Organizer
      第32回日本生体防御学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 結核菌に対する生体防御と炎症性サイトカイン2021

    • Author(s)
      松﨑吾朗, 藏根友美, 梅村正幸, 高江洲義一
    • Organizer
      第32回日本生体防御学会学術総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 結核菌エフェクタータンパク質Zmp1と会合するGRIM-19の機能解析2021

    • Author(s)
      藏根友美, 松永哲郎, 井田智章, 澤田和子, 梅村正幸, 赤池孝章, 松﨑吾朗, 高江洲義一
    • Organizer
      第5回抗酸菌研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] The effect of the deletion of the mycobacterial virulence factor Zmp1 on protective immunity2021

    • Author(s)
      Masasyuki Umemura, Sohkichi Matsumoto, Tomomi Kurane, Giichi Takaesu, Goro Matsuzaki
    • Organizer
      第50回日本免疫学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] GRIM-19 is a target of mycobacterial Zn2+metalloprotease 1 and indispensable for NLRP3 inflammasome activation2021

    • Author(s)
      Tomomi Kurane, Masasyuki Umemura, Masaaki Nakayama, Naoya Ohara, Goro Matsuzaki
    • Organizer
      第50回日本免疫学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 結核菌エフェクタータンパク質によるIL-1β産生阻害の分子機序2021

    • Author(s)
      藏根友美,高江洲義一,澤田和子,梅村正幸,松﨑吾朗
    • Organizer
      第94回日本細菌学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Dispensable role of chemokine receptors in migration of mycobacterial antigen-specific CD4+ T cells into mycobacteria-infected lung2020

    • Author(s)
      Masayuki Umemura, Masatoshi Yamasaki, Toshiki Tamura, and Goro Matsuzaki
    • Organizer
      104th ANNUAL MEETING OF THE AMERICAN ASSOCIATION OF IMMUNOLOGISTS
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Chemokine receptors in the migration of mycobacterial antigen-specific T cells into the infected lung2020

    • Author(s)
      Masayuki Umemura, Masatoshi Yamasaki, Toshiki Tamura, Goro Matsuzaki
    • Organizer
      第93回日本細菌学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Identification and functional analysis of a host protein targeted by mycobacterial effector Zmp12020

    • Author(s)
      Giichi Takaesu, Masayuki Umemura, Goro Matsuzaki
    • Organizer
      第93回日本細菌学会総会
    • Related Report
      2020 Research-status Report 2019 Research-status Report
  • [Presentation] A molecular mechanism of IL-1b inhibition by mycobacterial effector protein2020

    • Author(s)
      Tomomi Kurane, Kazuko Sawada, Giichi Takaesu, Masayuki Umemura, Goro Matsuzaki
    • Organizer
      第93回日本細菌学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 結核菌由来のエフェクタータンパク質によるIL-1β産生阻害の分子機序2020

    • Author(s)
      高江洲義一,藏根友美,澤田和子,西村明,松永哲郎,井田智章,梅村正幸,赤池孝章,松﨑吾朗
    • Organizer
      第31回日本生体防御学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] A molecular mechanism of IL-1β inhibition by mycobacterial effector protein2020

    • Author(s)
      Tomomi Kurane, Kazuko Sawada, Giichi Takaesu, Masayuki Umemura, Goro Matsuzaki
    • Organizer
      第93回日本細菌学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Chemokine receptors in the migration of mycobacterial antigen-specific T cells into the infected lung.2020

    • Author(s)
      Masayuki Umemura, Masatoshi Yamasaki, Toshiki Tamura, Goro Matsuzaki
    • Organizer
      第93回日本細菌学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Effects of zinc metalloprotease-1 on innate and Th1/Th17 immunity during lung mycobacterial infection.2019

    • Author(s)
      Msayuki Umemura, Naoko Teruya, Giichi Takaesu, Naoya Ohara, Goro Matsuzaki
    • Organizer
      第92回日本細菌学会総会
    • Related Report
      2019 Research-status Report 2018 Research-status Report
  • [Presentation] A molecular mechanism of IL-1β inhibition by mycobacterial effector protein.2019

    • Author(s)
      Tomomi Kurane, Kazuko Sawada, Giichi Takaesu, Masayuki Umemura, Goro Matsuzaki
    • Organizer
      第92回日本細菌学会総会
    • Related Report
      2019 Research-status Report 2018 Research-status Report
  • [Presentation] 病原因子Zmp1欠損マイコバクテリアによるT細胞免疫応答への影響2019

    • Author(s)
      梅村正幸, 藏根友美, 中山真彰, 大原直也, 高江洲義一, 松﨑吾朗
    • Organizer
      第84回 日本インターフェロン・サイトカイン学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 結核菌エフェクタータンパク質によるIL-1β産生阻害の分子機序2019

    • Author(s)
      藏根友美, 澤田和子, 高江洲 義一, 梅村正幸, 松﨑吾朗
    • Organizer
      第30回日本生体防御学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] BCG感染肺由来TcR γδ T細胞の抗原特異的IL-17A産生メカニズムの解明2019

    • Author(s)
      梅村正幸, 飯村澪, 高江洲義一, 松﨑吾朗
    • Organizer
      第30回日本生体防御学会学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 結核菌(Mtb)感染肺へのケモカインレセプター(CkR)非依存的なMtb抗原特異的CD4+T細胞の動2019

    • Author(s)
      松﨑吾朗,山崎雅俊,田村敏生,梅村正幸
    • Organizer
      第72回日本細菌学会九州支部総会
    • Related Report
      2019 Research-status Report
  • [Presentation] マイコバクテリア病原因子Zmp1の自然免疫およびT細胞免疫応答への影響2019

    • Author(s)
      梅村正幸, 木村倫和, 岩橋晃平, 照屋尚子, 藏根友美, 中山真彰, 大原直也, 高江洲義一, 松﨑吾朗
    • Organizer
      第60回日本熱帯医学会大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 結核菌エフェクタータンパク質によるIL-1β産生阻害の分子機序2019

    • Author(s)
      高江洲義一, 藏根友美, 澤田和子, 梅村正幸, 松﨑吾朗
    • Organizer
      第60回日本熱帯医学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Mechanism of mycobacteria specific IL-17A production of BCG infected lung-derived TcR γδ T cells.2019

    • Author(s)
      Masayuki Umemura, Mio Iimura, Tomomi Kurane, Giichi Takaesu, Goro Matsuzaki
    • Organizer
      第43回日本免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 結核菌感染におけるIL-17サイトカインファミリーの防御機構とその応用2019

    • Author(s)
      梅村正幸
    • Organizer
      第8回実験動物科学シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Effects of mycobacteria-derived Zmp1 on innate and T-cell immune responses.2019

    • Author(s)
      Masayuki Umemura
    • Organizer
      The 53rd United States-Japan Cooperative Medical Science Program: Mycobacterial Panel Meeting 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 自然免疫およびT細胞免疫応答へのBCG由来病原因子Zmp1の影響2018

    • Author(s)
      梅村正幸, 木村倫和, 岩橋晃平, 照屋尚子, 高江洲義一, 松﨑吾朗
    • Organizer
      第29回日本生体防御学会学術総会,
    • Related Report
      2018 Research-status Report
  • [Presentation] 結核菌の分泌タンパク質Zmp1によるIL-1β産生阻害機序2018

    • Author(s)
      高江洲義一, 藏根友美, 平安座啓, 山田綾太郎, 梅村正幸, 松﨑吾朗
    • Organizer
      第29回日本生体防御学会学術総会,
    • Related Report
      2018 Research-status Report
  • [Presentation] 肺結核に対するIL-17サイトカイン・ファミリーの防御免疫への関与2018

    • Author(s)
      梅村正幸
    • Organizer
      沖縄感染免疫シンポジウム2018
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] マイコバクテリア感染肺に誘導されるIL-17A産生細胞の多様性2018

    • Author(s)
      梅村正幸, 儀間香南子, 高江洲義一, 中江進, 岩倉洋一郎, 松﨑吾朗
    • Organizer
      第83回日本インターフェロン・サイトカイン学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] A mycobacterial virulence factor Zmp1 interferes with NLRP3 inflammasome activation by targeting host mitochondrial protein.2018

    • Author(s)
      Giichi Takaesu, Tomomi Kurane, Masayuki Umemura, Goro Matsuzaki
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Effects of mycobacteria-derived zinc-dependent metalloprotease-1 (Zmp1) on innate and T-cell immune response.2018

    • Author(s)
      Masayuki Umemura, Giichi Takaesu, Goro Matsuzaki
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Remarks] 琉球大学熱帯生物圏研究センター

    • URL

      https://tbc.skr.u-ryukyu.ac.jp

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
  • [Remarks] 琉球大学熱帯生物圏研究センター

    • URL

      http://www.tbc.u-ryukyu.ac.jp/

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi