Immune evasion strategy of pathogenic fungi via inhibitory receptors

• Project/Area Number: 17K08888
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Saga University
• Principal Investigator: Miyake Yasunobu 佐賀大学, 医学部, 准教授 (10392143)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: レクチン受容体 / Siglec / 脂質リガンド / 免疫抑制型受容体 / 免疫回避機構

Outline of Final Research Achievements

Siglecs are a family of cell-surface immune receptors that bind to sialic acid at terminal glycan residues. We found that Siglec5 and Siglec14 recognize pathogenic fungi, Trichophyton spp. Trichophyton spp modulated host immune responses via Siglec5 and 14. Biochemical approaches revealed that the Siglec ligands are fungal alkanes and triacylglycerols. Furthermore, Siglec5 weakly recognized several endogenous lipids. Among them, cardiolipin and 5-PAHSA exhibited potent ligand activity on Siglec5. Further, the hydrophobic stretch in the Siglec5 N terminus region was found to be required for efficient recognition of these lipids.

Academic Significance and Societal Importance of the Research Achievements

これまでSiglecはシアル酸を認識する受容体として様々な生命現象に関与することが明らかにされてきた。が、本研究によりSiglecが脂質リガンドを認識することが明らかになったことで、Siglecの生理的・病理的機能の理解が新たな方向へと進展する可能性が期待される。

Research Products

• [Journal Article] Immune recognition of pathogen-derived glycolipids through Mincle (2020)
  • Author(s): Miyake, Y., Sho Yamasaki
  • Journal Title: Lectins in Host Defense against Microbial Infections Volume: 1204 Pages: 31-56
  • DOI: 10.1007/978-981-15-1580-4_2
  • ISBN: 9789811515798, 9789811515804
• [Journal Article] Identification of lipophilic ligands of Siglec5 and -14 that modulate innate immune responses (2019)
  • Author(s): Suematsu, R. Miyamoto, T. Saijo, S. Yamasaki, S. Tada, Y. Yoshida, H. Miyake, Y.
  • Journal Title: Int J Mol Sci Volume: 45 Issue: 45 Pages: 16776-16788
  • DOI: 10.1074/jbc.ra119.009835
  • Peer Reviewed / Open Access
• [Journal Article] Essential roles of C-type lectin Mincle in induction of neuropathic pain in mice. (2019)
  • Author(s): Asako Ishikawa, Yasunobu Miyake, Kimiko Kobayashi, Yuzo Murata, Sayaka Iizasa, Ei’ichi Iizasa, Sho Yamasaki, Naomi Hirakawa, Hiromitsu Hara, Hiroki Yoshida, Toshiharu Yasaka
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 872-872
  • DOI: 10.1038/s41598-018-37318-8
  • Peer Reviewed / Open Access
• [Journal Article] Siglec5,14は白癬菌トリコフィトン属を認識して免疫応答を制御する (2019)
  • Author(s): 三宅靖延
  • Journal Title: 臨床免疫・アレルギー科 Volume: 71 Pages: 272-277
• [Journal Article] A Flow Cytometry Method for Dissecting the Cell Differentiation Process of Entamoeba Encystation (2018)
  • Author(s): Mi-ichi Fumika、Miyake Yasunobu、Tam Vo Kha、Yoshida Hiroki
  • Journal Title: Frontiers in Cellular and Infection Microbiology Volume: 8 Pages: 250-250
  • DOI: 10.3389/fcimb.2018.00250
  • Peer Reviewed / Open Access
• [Journal Article] Apaf1 plays a negative regulatory role in T cell responses by suppressing activation of antigen-stimulated T cells. (2018)
  • Author(s): Tong, H., Miyake, Y., Mi-Ichi, F., Iwakura, Y., Hara, H. and Yoshida, H.
  • Journal Title: PLoS One Volume: 13 Issue: 3 Pages: 0195119-0195119
  • DOI: 10.1371/journal.pone.0195119
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Spontaneous chondroma formation in CD2-Cre-driven Erk-deficient mice (2017)
  • Author(s): Shiokawa Moe、Lu Xiuyuan、Miyake Yasunobu、Ishikawa Eri、Pages Gilles、Pouyssegur Jacques、Ogata Masato、Yamasaki Sho
  • Journal Title: International Immunology Volume: 29 Issue: 10 Pages: 479-485
  • DOI: 10.1093/intimm/dxx056
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] パターン認識受容体としてのC型レクチン受容体 (2017)
  • Author(s): 三宅靖延
  • Journal Title: 臨床免疫アレルギー科 Volume: 67 Pages: 636-641
  • NAID: 40021232421
• [Presentation] Identification of novel lipophilic ligands of Siglec5 and 14 that modulate innate immune responses. (2020)
  • Author(s): Yasunobu Miyake
  • Organizer: 第8回ITAM Workshop
• [Presentation] Identification of novel lipophilic ligands of Siglec5 and 14 that modulate innate immune responses. (2019)
  • Author(s): Yasunobu Miyake, Rie Suematsu and Hiroki Yoshida
  • Organizer: 第48回 日本免疫学会学術集会
• [Presentation] マクロファージの現代的意義とその研究手法 (2019)
  • Author(s): 三宅靖延
  • Organizer: 第31回 日本神経免疫学会学術集会
  • Invited
• [Presentation] シアル酸認識受容体Siglecの新規脂溶性リガンドの発見 (2019)
  • Author(s): 三宅靖延、末松梨絵、吉田裕樹
  • 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
• [Presentation] Periodontal pathogen P. gingivalis modulates host immunity through Siglec receptors. (2019)
  • Author(s): Yasunobu Miyake
  • Organizer: 第7回ITAM Workshop
• [Presentation] Porphyromonas gingivalis negatively regulates host immune responses through inhibitory receptor, Siglec (2018)
  • Author(s): Yasunobu Miyake, Sho Yamasaki and Hiroki Yoshida
  • Organizer: 第47回 日本免疫学会学術集会
• [Presentation] Immunosuppressive receptor, Siglec5 recognizes lipophilic ligands extracted from pathogenic fungus, Trichophyton mentagrophytes (2018)
  • Author(s): Rie Suematsu, Yasunobu Miyake, Shinobu Saijo and Hiroki Yoshida
  • Organizer: 第47回 日本免疫学会学術集会
• [Presentation] Apaf1 plays a negative regulatory role in T cell responses by suppressing activation of antigen-stimulated T cells (2018)
  • Author(s): Tong H, Miyake Y, Mi-ichi F, Iwakura Y, Hara H, Yoshida H
  • Organizer: The 11th International congress on Autoimmunity
  • Int'l Joint Research
• [Presentation] Novel immune evasion strategy of P. gingivalis via inhibitory receptor, Siglec. (2018)
  • Author(s): Miyake Y, Yoshida H
  • Organizer: 6th Annual Meeting of the International Cytokine & Interferon Society (ICIS)
  • Int'l Joint Research
• [Presentation] Immune evasion strategy of P. gingivalis via inhibitory receptor, Siglec (2018)
  • Author(s): Yasunobu Miyake
  • Organizer: 第6回ITAM Workshop
• [Presentation] CD2-Cre Tgを用いたErk欠損マウスにおける軟骨の過増殖 (2017)
  • Author(s): 塩川 萌、陸 修遠、三宅靖延、緒方 正人、山崎 晶
  • Organizer: 第3回 日本骨免疫学会
• [Presentation] Pathogenic fungus, Trichophyton mentagrophytes negatively regulates host immune responses via Siglec receptors (2017)
  • Author(s): Yasunobu Miyake, Eri Suematsu, Shinobu Saijo, Sho Yamasaki and Hiroki Yoshida
  • Organizer: The 5th Annual Meeting of the International Cytokine and Interferon Society
  • Int'l Joint Research
• [Presentation] Immunosuppressive receptor, Siglec binds to pathogenic fungus, Trichophyton mentagrophytes, and negatively regulates host immune responses (2017)
  • Author(s): Yasunobu Miyake, Eri Suematsu, Shinobu Saijo, Sho Yamasaki and Hiroki Yoshida
  • Organizer: 第46回 日本免疫学会学術集会
• [Book] 次世代アジュバント開発のためのメカニズム解析と安全性評価 (2017)
  • Author(s): 吉田裕樹、三宅靖延、原博満
  • Total Pages: 355
  • Publisher: CMC出版
  • ISBN: 9784781312385