Molecular mechanisms of non specific T cell response upon malaria

• Project/Area Number: 15K08520
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Gunma University
• Principal Investigator: SUZUE Kazutomo 群馬大学, 大学院医学系研究科, 講師 (00333485)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: マラリア / 免疫抑制 / T細胞 / ATP / ヌクレオチド / アデノシン / プリン受容体 / ヌクレオシド / 活性化制御 / 細胞外ATP / P2X7 / P2Y2 / マウス / 貧血 / 活性化 / P2レセプター / サイトカイン

Outline of Final Research Achievements

A specificity is the most important in the immune system, and if this immunological rule is violated, immune cells that are unrelated to the pathogen become activated upon infection. We found that in malaria infection, the immune response is nonspecifically activated and suppressed. This characteristic T cell response was inhibited by blocking ATP release from red blood cells. Furthermore, it has been suggested that adenosine, which is a metabolite of ATP, suppresses the immune response nonspecifically.

Academic Significance and Societal Importance of the Research Achievements

マラリア感染における非特異的免疫抑制の分子メカニズムの解明に近づく結果が得られた。この結果から、マラリア流行地におけるほかの感染症の複合感染の重症化メカニズムや、逆にマラリア流行地ではほとんど見られず、先進国において問題となっているアレルギーや自己免疫疾患の治療戦略に対するヒントが得られたと考えている。本研究をさらに発展させることで、マラリア患者の複合感染症対策や、先進国におけるアレルギー・自己免疫疾患対策だけでなく、新規マラリア治療戦略の発展も期待できるものである。

Research Products

• [Journal Article] Differentiation of malignant tumours from granulomas by using dynamic [(18)F]-fluoro-L-α-methyltyrosine positron emission tomography. (2015)
  • Author(s): Yamaguchi A, Hanaoka H, Fujisawa Y, Zhao S, Suzue K, Morita A, Tominaga H, Higuchi T, Hisaeda H, Tsushima Y, Kuge Y, Iida Y.
  • Journal Title: EJNMMI Res. Volume: 5 Issue: 1 Pages: 29-29
  • DOI: 10.1186/s13550-015-0109-z
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A transient resistance to blood-stage malaria in interferon-γ-deficient mice through impaired production of the host cells preferred by malaria parasites. (2015)
  • Author(s): Okada H, Suzue K, Imai T, Taniguchi T, Shimokawa C, Onishi R, Hirata J, Hisaeda H.
  • Journal Title: Front Microbiol. Volume: 6 Pages: 600-600
  • DOI: 10.3389/fmicb.2015.00600
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Plasmodium berghei ANKA causes intestinal malaria associated with dysbiosis (2015)
  • Author(s): Taniguchi T, Miyauchi E, Nakamura S, Hirai M, Suzue K, Imai T, Nomura T, Handa T, Okada H, Shimokawa C, Onishi R, Olia A, Hirata J, Tomita H, Ohno H, Horii T, Hisaeda H
  • Journal Title: Scientific Reports Volume: 5:15699 Issue: 1 Pages: 1-12
  • DOI: 10.1038/srep15699
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Pathogen non-specific bystander T cells were attenuated upon infection (2016)
  • Author(s): K. Suzue, H. Amano, T. Taniguchi, C. Shimokawa, O. Alex, R. Onishi, H. Hisaeda
  • Organizer: International Congress of Immunology 2016
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] Pathogen non-specific bystander T cells were attenuated upon infection with malaria parasites (2016)
  • Author(s): Kazutomo Suzue, Hiroo Amano, Tomoyo Taniguchi, Chikako Shimokawa, Alex Olia, Risa Onishi, Hajime Hisaeda
  • Organizer: The International Congress of Immunology (ICI) 2016
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2016-08-21
  • Int'l Joint Research