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Regulation of innate immune response to mycobacteria through the recognition of immunoregulating cell wall lipids by ITAM-coupled receptors

Research Project

Project/Area Number 15H04729
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionKagoshima University

Principal Investigator

hara hiromitsu  鹿児島大学, 医歯学域医学系, 教授 (20392079)

Co-Investigator(Renkei-kenkyūsha) YAMASAKI Sho  大阪大学, 微生物病研究所, 教授 (40312946)
MATSUZAKI Goro  琉球大学, 熱帯生物圏研究センター, 教授 (30229455)
KIYOHARA Hideyasu  日本BCG研究所, 第一研究科部, 研究員 (10514581)
IIZASA Eiichi  鹿児島大学, 医歯学総合研究科, 助教 (20631998)
MAENAKA Katsumi  北海道大学, 薬学研究科, 教授 (10322752)
MIYAZAKI Jun  国際医療福祉大学, 医学部, 教授 (10550246)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords抗酸菌 / ITAM / CLR / 自然免疫 / マクロファージ / 脂質 / 結核 / C型レクチン / 感染症 / 細菌 / 免疫学
Outline of Final Research Achievements

Mycobacterial cell wall lipids have immune-stimulating or modulating activities. Several C-type lectin receptors associated with immunoreceptor tyrosine-based activation motif (ITAM)-bearing adaptor FcRγ recognize mycobacterial glycolipids and play important roles in anti-mycobacterial immunity. On the other hand, previous studies suggested immunomodulatory role of DAP12, another ITAM-bearing adaptor, in anti-mycobacterial immunity, implicating the presence of DAP12-associated receptors that might recognize immunomodulatory ligands in mycobacteria. We identified two novel ITAM-coupled receptors that recognize the immunomodulatory mycobacterial lipids mycolate (MA) and phenolic glycolipids (PGL). Deficiency of these receptors in macrophages abrogated the response to these lipids. Activation of the MA receptor recruited mycobacterium permissive macrophages. Loss of the MA receptor enhanced mincle-induced inflammation in vivo and accelerated clearance of M. bovis BCG infected in mice.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (14 results)

All 2017 2016 2015

All Journal Article (2 results) (of which Peer Reviewed: 1 results) Presentation (12 results) (of which Int'l Joint Research: 2 results,  Invited: 6 results)

  • [Journal Article] Interleukin-27-Producing CD4(+) T Cells Regulate Protective Immunity during Malaria Parasite Infection.2016

    • Author(s)
      Kimura D, Miyakoda M, Kimura K, Honma K, Hara H, Yoshida H, Yui K
    • Journal Title

      Immunity

      Volume: 44 Issue: 3 Pages: 672-682

    • DOI

      10.1016/j.immuni.2016.02.011

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Carma1クラスターによる抗原受容体シグナルの制御2015

    • Author(s)
      原博満
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 64 Pages: 398-403

    • NAID

      40020622957

    • Related Report
      2015 Annual Research Report
  • [Presentation] Two ITAM-coupled receptors recognizing mycobacterial mycolic acid-containing lipids and having the different role2017

    • Author(s)
      Iizasa E, Uematsu T, Kiyohara H, Chuma Y, Kubota M, Umemura M, Matsuzaki G, Yamasaki S, Yoshida H, Hara H
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ITAM共役受容体による抗酸菌脂質の認識と自然免疫応答の制御2017

    • Author(s)
      原博満
    • Organizer
      第36回日本認知症学会学術集会シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Two distinct ITAM-coupled receptors recognize mycobacterial mycolic acid-containing lipids and differently regulate immune responses2017

    • Author(s)
      Iizasa E, Uematsu T, Kiyohara H, Chuma Y, Kubota M, Umemura M, Matsuzaki G. Yamasaki S., Yoshida H, Hara H
    • Organizer
      Cytokines 2017 (5th Annual meeting of the International Cytokine & Interferon Society
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ITAM共役型パターン認識受容体による抗酸菌脂質の認識と自然免疫応答の制御2017

    • Author(s)
      原博満、飯笹英一
    • Organizer
      第27回樹状細胞研究会シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Regulation of innate immune response to mycobacteria through DAP12 versus FcRga-coupled myeloid receptors that recognize different mycolic acid-containing lipids2016

    • Author(s)
      Ei’ichi Iizasa, Takayki Uematsu, Mio Kubota, Hideyasu Kiyohara, Yasushi Chuma, Goro Matsuzaki, Sho Yamasaki, Hiroki Yoshida, Hiromitsu Hara
    • Organizer
      ICI2013
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2016-08-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ITAM関連パターン認識受容体による抗酸菌認識と自然免疫応答の制御2016

    • Author(s)
      原博満、飯笹英一
    • Organizer
      日本生体防御学会学術総会シンポジウム
    • Place of Presentation
      九州大学医学部視聴覚ホール(福岡県福岡市)
    • Year and Date
      2016-07-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] 結核菌のミコール酸含有脂質を認識する2つの受容体IgSFR2とMincleによる免疫制御2016

    • Author(s)
      飯笹英一、植松崇之、久保田未央、清原秀泰、中馬康志、松崎吾朗、山崎晶、吉田裕樹、原博満
    • Organizer
      第81回インターフェロン・サイトカイン学会シンポジウム
    • Place of Presentation
      長崎大学ポンペ会館(長崎県長崎市)
    • Year and Date
      2016-05-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] ITAM関連受容体によるパターン認識と自然免疫応答2015

    • Author(s)
      原博満
    • Organizer
      The 44th annual meeting of the Japanese Society for Immunology
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 脂質センサー型ITAM受容体による結核自然免疫応答の制御.2015

    • Author(s)
      原博満、飯笹英一、清原秀泰、中馬康志、矢野郁也、植松崇之、久保田未央、梅村正幸、山崎晶、松崎吾朗、吉田裕樹
    • Organizer
      沖縄感染免疫シンポジウム
    • Place of Presentation
      琉球大学医学部基礎講義実習棟101(沖縄県中頭郡西原町)
    • Year and Date
      2015-07-31
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 脂質認識型ITAM受容体による結核菌の認識と自然免疫応答2015

    • Author(s)
      原博満、飯笹英一、清原秀泰、中馬康志、矢野郁也、植松崇之、久保田未央、梅村正幸、山崎晶、松崎吾朗、吉田裕樹
    • Organizer
      第80回日本インターフェロン・サイトカイン学会大会シンポジウム
    • Place of Presentation
      東京工業大学蔵前会館(東京都目黒区)
    • Year and Date
      2015-07-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 自然免疫ITAM関連受容体による結核菌脂質の認識と免疫応答2015

    • Author(s)
      原博満、飯笹英一、清原秀泰、中馬康志、矢野郁也、植松崇之、久保田未央、梅村正幸、山崎晶、松崎吾朗、吉田裕樹
    • Organizer
      第26回日本生体防御学会学術総会シンポジウム
    • Place of Presentation
      台東区生涯学習センター(東京都台東区)
    • Year and Date
      2015-07-10
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] マウス創傷治癒過程におけるCARD9遺伝子欠損の影響2015

    • Author(s)
      上松野りな、鈴木愛子、菅野恵美、丹野寛大、高木尚之、石井恵子、原博満、丸山良子、川上和義,館正弘
    • Organizer
      第26回日本生体防御学会学術総会
    • Place of Presentation
      台東区生涯学習センター(東京都台東区)
    • Year and Date
      2015-07-10
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2019-12-27  

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