Host-bacteria interactions through immune evasion mechanism

• Project/Area Number: 19H03468
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: Kanazawa University
• Principal Investigator: Hirayasu Kouyuki 金沢大学, 先進予防医学研究センター, 准教授 (30585170)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 免疫逃避機構 / 宿主細菌相互作用 / 免疫レセプター / アリル多様性 / LILR

Outline of Research at the Start

近年の抗菌薬やワクチンの開発により、現代では様々な細菌感染症を治療および予防することができる。しかし、抗菌薬がなかった時代では、多くの細菌感染症が致死的であった。本研究では、細菌が免疫から逃れる何らかの仕組みにより宿主の免疫応答を妨げているのではないかと考え、このような細菌の免疫逃避機構および宿主の細菌に対する免疫応答を明らかにすることを目的とする。

Outline of Final Research Achievements

Immune system plays an important role in host defense against pathogens and tumor cells. However, it is known that pathogens and tumor cells have acquired various immune evasion mechanisms to escape from the host immune system. This study revealed that certain immune inhibitory receptors recognize specific bacteria and that both immune inhibitory receptors and their bacterial ligands show genetic diversity. These results suggest that host and bacteria have coevolved through immune inhibitory receptor-mediated bacterial immune evasion mechanisms.

Academic Significance and Societal Importance of the Research Achievements

現代では、抗菌薬やワクチンの開発により、様々な細菌感染症に対して治療を行うことができるようになった。しかし、抗菌薬やワクチンがなかった時代では、病原細菌は致死的な感染症を引き起こしていた。本来免疫が細菌を排除する役割を担っているが、なぜ宿主免疫は病原細菌を排除できない場合があるのだろうか。本研究では、免疫を抑制する免疫抑制化レセプターが細菌を認識してしまうことで免疫にブレーキがかかる可能性が示された。

Research Products

• [Journal Article] Characterization of LILRB3 and LILRA6 allelic variants in the Japanese population (2021)
  • Author(s): Hirayasu K, Sun J, Hasegawa G, Hashikawa Y, Hosomichi K, Tajima A, Tokunaga K, Ohashi J, Hanayama R.
  • Journal Title: Journal of Human Genetics Volume: 印刷中 Issue: 7 Pages: 739-748
  • DOI: 10.1038/s10038-021-00906-0
  • Peer Reviewed
• [Journal Article] Plasmodium falciparum RIFIN is a novel ligand for inhibitory immune receptor LILRB2. (2021)
  • Author(s): Sakoguchi A, Saito F, Hirayasu K, Shida K, Matsuoka S, Itagaki S, Nakai W, Kohyama M, Suenaga T, Iwanaga S, Horii T, Arase H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 548 Pages: 167-173
  • DOI: 10.1016/j.bbrc.2021.02.033
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular mechanism of the recognition of bacterially cleaved immunoglobulin by the immune regulatory receptor LILRA2 (2020)
  • Author(s): Yamazaki Rika、Furukawa Atsushi、Hirayasu Kouyuki、Yumoto Kohei、Fukuhara Hideo、Arase Hisashi、Maenaka Katsumi
  • Journal Title: Journal of Biological Chemistry Volume: 295 Issue: 28 Pages: 9531-9541
  • DOI: 10.1074/jbc.ra120.013354
  • NAID: 120007116484
  • Peer Reviewed
• [Journal Article] Genotype and phenotype analysis of patients with pediatric cutaneous mastocytosis, especially wild‐type KIT patients (2020)
  • Author(s): Arase Noriko、Wataya‐Kaneda Mari、Murota Hiroyuki、Nakagawa Yukinobu、Yamaoka Toshifumi、Itoi‐Ochi Saori、Hirayasu Kouyuki、Arase Hisashi、Fujimoto Manabu、Katayama Ichiro
  • Journal Title: The Journal of Dermatology Volume: 47 Issue: 4 Pages: 426-429
  • DOI: 10.1111/1346-8138.15266
  • Peer Reviewed
• [Presentation] Genetic and functional diversity of leukocyte immunoglobulin-like receptor family in humans (2021)
  • Author(s): Hirayasu Kouyuki
  • Organizer: 3rd Japan-Germany Symposium on Advanced Preventive Medicine 2021
  • Int'l Joint Research / Invited
• [Presentation] LILRファミリーにみる遺伝的・機能的多様性 (2020)
  • Author(s): 平安恒幸
  • Organizer: 日本人類遺伝学会第65回大会
  • Invited
• [Presentation] Characterization of allelic and functional variations of LILRB3 and LILRA6 in the Japanese population. (2020)
  • Author(s): Sun J, Hirayasu K, Hanayama R.
  • Organizer: 第93回日本生化学会大会
• [Presentation] 免疫逃避機構からみた宿主と微生物の相互作用 (2019)
  • Author(s): 平安 恒幸
  • Organizer: 第92回日本細菌学会総会
  • Invited
• [Remarks] 科研費 研究成果トピックス
  • URL: https://www.jsps.go.jp/j-grantsinaid/37_topics/data/00178-13301-30585170.pdf