Clarification of the mechanisms of acquired tick resistance

• Project/Area Number: 17K15719
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: YOSHIKAWA Soichiro 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (10549926)
• Research Collaborator: KANUKA Hirotaka ; YAMAJI Kayoko ; ISHIWATA Kenji ; WATANABE Naohiro
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 獲得免疫 / 好塩基球 / ヒスタミン / IL-3 / 細胞浸潤 / 感染症 / マスト細胞 / マダニ / メモリーT細胞 / 免疫学 / アレルギー・ぜんそく

Outline of Final Research Achievements

Ticks are blood-sucking arthropods that can transmit various pathogenic organisms to host animals and humans, causing serious infectious diseases. Several species of animals develop resistance to tick-feeding after single or multiple tick infestation. Basophils reportedly play key roles in the manifestation of acquired tick resistance, but it remains ill-defined how they were recruited and how they contribute to it. In present study, we demonstrated that skin-resident memory CD4 T cells are stimulated with tick antigens to produce IL-3 that in turn promotes the recruitment of IgE-armed basophils from the peripheral blood to the tick-feeding site. Moreover, IgE-armed basophils are activated with tick antigens to release histamine that acts on keratinocyte, resulting in epidermal hyperplasia that may interfere with tick attachment or blood feeding in the skin, and hence contribute to acquired tick resistance.

Academic Significance and Societal Importance of the Research Achievements

SFTSをはじめとするマダニ媒介性感染症には致死性の高いものもあり、昨今わが国でも大きな問題となっている。マダニ媒介性感染症を予防する最も有効な手段は、マダニに刺されないことである。しかし、殺ダニ剤を用いた対処では、薬剤耐性マダニの出現や環境被害の影響があり、多くの問題が残っていた。古くからマダニに対する免疫を持った動物ではこの感染症の伝播が起こりにくいことが知られており、マダニに対する免疫が注目されていた。本研究により、マダニに対する免疫のメカニズムの一端が解明された。本研究成果は、マダニ吸血に対する有効的なワクチンの開発に活かすことができ、学術・社会的な面からも非常に意義のある研究である。

Research Products

• [Journal Article] Crucial Role for Basophils in Acquired Protective Immunity to Tick Infestation (2018)
  • Author(s): Karasuyama Hajime、Tabakawa Yuya、Ohta Takuya、Wada Takeshi、Yoshikawa Soichiro
  • Journal Title: Frontiers in Physiology Volume: 9
  • DOI: 10.3389/fphys.2018.01769
  • Peer Reviewed / Open Access
• [Journal Article] How do basophils contribute to Th2 cell differentiation and allergic responses? (2018)
  • Author(s): Karasuyama Hajime、Miyake Kensuke、Yoshikawa Soichiro、Kawano Yohei、Yamanishi Yoshinori
  • Journal Title: International Immunology Volume: 30 Issue: 9 Pages: 391-396
  • DOI: 10.1093/intimm/dxy026
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Basophils trigger emphysema development in a murine model of COPD through IL-4?mediated generation of MMP-12?producing macrophages (2018)
  • Author(s): Shibata Sho、Miyake Kensuke、Tateishi Tomoya、Yoshikawa Soichiro、Yamanishi Yoshinori、Miyazaki Yasunari、Inase Naohiko、Karasuyama Hajime
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 115 Issue: 51 Pages: 13057-13062
  • DOI: 10.1073/pnas.1813927115
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Aggregation makes a protein allergenic at the challenge phase of basophil-mediated allergy in mice (2018)
  • Author(s): Nagao Toshihisa、Yamanishi Yoshinori、Miyake Kensuke、Teranishi Mio、Takahashi Saori、Yoshikawa Soichiro、Kawano Yohei、Karasuyama Hajime
  • Journal Title: International Immunology Volume: 31 Issue: 1 Pages: 41-49
  • DOI: 10.1093/intimm/dxy062
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Histamine Released From Skin-Infiltrating Basophils but Not Mast Cells Is Crucial for Acquired Tick Resistance in Mice (2018)
  • Author(s): Tabakawa Yuya、Ohta Takuya、Yoshikawa Soichiro、Robinson Elisabeth J.、Yamaji Kayoko、Ishiwata Kenji、Kawano Yohei、Miyake Kensuke、Yamanishi Yoshinori、Ohtsu Hiroshi、Adachi Takahiro、Watanabe Naohiro、Kanuka Hirotaka、Karasuyama Hajime
  • Journal Title: Frontiers in Immunology Volume: 9
  • DOI: 10.3389/fimmu.2018.01540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Multifaceted roles of basophils in health and disease (2017)
  • Author(s): Karasuyama H, Miyake K, Yoshikawa S, Yamanishi Y
  • Journal Title: J Allergy Clin Immunol Volume: S0091-6749 Issue: 2 Pages: 31894-31898
  • DOI: 10.1016/j.jaci.2017.10.042
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Skin CD4+ Memory T Cells Play an Essential Role in Acquired Anti-Tick Immunity through Interleukin-3-Mediated Basophil Recruitment to Tick-Feeding Sites (2017)
  • Author(s): Ohta Takuya、Yoshikawa Soichiro、Tabakawa Yuya、Yamaji Kayoko、Ishiwata Kenji、Shitara Hiroshi、Taya Choji、Oh-hora Masatsugu、Kawano Yohei、Miyake Kensuke、Yamanishi Yoshinori、Yonekawa Hiromichi、Watanabe Naohiro、Kanuka Hirotaka、Karasuyama Hajime
  • Journal Title: Frontiers in Immunology Volume: 8 Pages: 1348-1348
  • DOI: 10.3389/fimmu.2017.01348
  • Peer Reviewed / Open Access
• [Journal Article] Differential usage of COX-1 and COX-2 in prostaglandin production by mast cells and basophils (2017)
  • Author(s): Bando, T., Fujita, S., Nagano, N., Hayashi, A., Yoshikawa, S., Yamanishi, Y., Minami, M., Tada, H., Kishikawa, K., and Karasuyama, H.
  • Journal Title: Biochem Biophys Rep. Volume: 10 Pages: 82-87
  • DOI: 10.1016/j.bbrep.2017.03.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Histamine released from skin-infiltrating basophils but not mast cells is crucial for acquired tick resistance in mice (2018)
  • Author(s): Yoshikawa S. Tabakawa Y. Ohta T. Yamaji K. Ishiwata K. Kawano Y. Yamanishi Y. Ohtsu H. Adachi T. Watanabe N. Kanuka H. Karasuyama H.
  • Organizer: 日本免疫学会
• [Presentation] Prolonged Ca2+ influx via STIM2 is essential for cytokine-induced IL-4 production in basophil. (2017)
  • Author(s): Yoshikawa, S., Oh-hora, M., Miyake, K., Kawano, Yohei., Yamanishi, Y., Karasuyama, H
  • Organizer: The 46th Japanese Society for Immunology 2017
• [Presentation] Skin-resident memory CD4+ T cells play an essential role in acquired tick resistance through IL-3-mediated basophil recruitment (2017)
  • Author(s): OHTA Takuya, YOSHIKAWA Soichiro, YAMAJI Kayoko, ISHIWATA Kenji, TABAKAWA Yuya, KAWANO Yohei, YAMANISHI Yoshinori, WATANABE Naohiro, KANUKA Hirotaka, KARASUYAMA Hajime
  • Organizer: The 46th Japanese Society for Immunology 2017
• [Presentation] Histamine plays a critical role in acquired protective immunity against tick infestation (2017)
  • Author(s): TABAKAWA Yuya, OHTA Takuya, YOSHIKAWA Soichiro, YAMAJI Kayoko, ISHIWATA Kenji, KAWANO Yohei, YAMANISHI Yoshinori, WATANABE Naohiro, OHTSU Hiroshi, KANUKA Hirotaka, KARASUYAMA Hajime
  • Organizer: The 46th Japanese Society for Immunology 2017
• [Remarks] 「マダニ吸血を阻害する免疫物質の同定」
  • URL: http://www.tmd.ac.jp/archive-tmdu/kouhou/20180719_1.pdf