Analyses of the roles of CARD9-dependent innate immunity against protozoa infection

• Project/Area Number: 25460594
• 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: Yoshida Hiroki 佐賀大学, 医学部, 教授 (40260715)
• Co-Investigator(Kenkyū-buntansha): HARA Hiromitsu 鹿児島大学, 大学院医歯総合研究科, 教授 (20392079)
• Co-Investigator(Renkei-kenkyūsha): MIYAMOTO Tomofumi 九州大学, 薬学研究院, 准教授 (40182050)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 原虫 / 自然免疫 / CARD9 / 炎症性サイトカイン / Th1 / 受容体 / サイトカイン / 寄生虫 / ITAM受容体

Outline of Final Research Achievements

In this study, we examined the role of CARD9-dependent innate immunity against protozoa infection. When infected with Leishmania major, CARD9-deficient mice demonstrated impaired resistance to infection with reduced inflammatory cytokine production at an early phase and impairment of Th1 response induction at a late phase of infection. CARD9, thus, is important in the initial defense and subsequent induction of Th1 responses during protozoa infection. By taking advantage of an ITAM-receptor protein library, we identified a couple of protozoa-binding receptors. One of the candidate receptors is shown to recognize carbohydrate motif on the surface of L. major.

Research Products

• [Journal Article] Clustering of CARMA1 through SH3-GUK domain interactions is required for its activation of NF-kB signaling (2015)
  • Author(s): Hara, H., Yokosuka, T., Hirakawa, H., Ishihara, C., Yasukawa, S., Yamazaki, M., Koseki, H., Yoshida, H. and Saito, T.
  • Journal Title: Nat. Commun. Volume: 6 Issue: 1 Pages: 5555-5555
  • DOI: 10.1038/ncomms6555
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Entamoeba mitosomes play an important role in encystation by association with cholesteryl sulfate synthesis. (2015)
  • Author(s): Mi-ichi F, Miyamoto T, Takao S, Jeelani G, Hashimoto T, Hara H, Nozaki T, Yoshida H.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 112 Issue: 22 Pages: 11407-11412
  • DOI: 10.1073/pnas.1423718112
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Evidence that Entamoeba histolytica mitochondrial carrier family links mitosomal and cytosolic pathways through exchange of PAPS and ATP. (2015)
  • Author(s): Mi-ichi, F., Nozawa, A., Yoshida, H., Tozawa, Y., Nozaki, T.
  • Journal Title: Eukaryot Cell Volume: 14 Issue: 11 Pages: 1144-1150
  • DOI: 10.1128/ec.00130-15
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity (2015)
  • Author(s): Uematsu, T. Iizasa, E. Kobayashi, N. Yoshida, H. Hara, H.
  • Journal Title: Sci Rep Volume: 5 Issue: 1 Pages: 17577-17577
  • DOI: 10.1038/srep17577
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The immunobiology of interleukin-27 (2015)
  • Author(s): Yoshida, H. Hunter, C. A.
  • Journal Title: Annu Rev Immunol Volume: 33 Issue: 1 Pages: 417-43
  • DOI: 10.1146/annurev-immunol-032414-112134
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] IL-27 affects helper T cell responses via regulation of PGE2 production by macrophages. (2014)
  • Author(s): Y. Sato, H. Hara, T. Okuno, N. Ozaki, S. Suzuki, T. Yokomizo, T. Kaisho, H. Yoshida.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 451 Issue: 2 Pages: 215-221
  • DOI: 10.1016/j.bbrc.2014.07.096
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] EBI3 is pivotal for the initiation of experimental autoimmune uveitis. (2014)
  • Author(s): Takeda A, Hasegawa E, Fukuhara T, Hirakawa S, Yamada H, Yang Y, Yoshimura T, Hisatomi T, Oshima Y, Yoshida H, Sonoda KH, Ishibashi T
  • Journal Title: Exp Eye Res Volume: 125 Pages: 107-113
  • DOI: 10.1016/j.exer.2014.06.004
  • Peer Reviewed
• [Journal Article] An ITAM-Syk-CARD9 signaling axis triggers contact hypersensitivity by stimulating IL-1 production in dendritic cells (2014)
  • Author(s): Yasukawa. S., Miyazaki, Y., Yoshii, C., Nakaya, M., Ozaki, N., Toda, S., Kuroda, E., Ishibashi, K., Yasuda, T., Natsuaki, Y., Mi-ichi, F., Iizasa, E., Nakahara, T., Yamazaki, M., Kabashima, K., Iwakura, Y., Takai, T., Saito, T., Kurosaki, T., Malissen, B., Ohno, N., Furue, M., Yoshida, H., and Hara, H
  • Journal Title: Nature Comm Volume: 5 Issue: 1 Pages: 3755-3755
  • DOI: 10.1038/ncomms4755
  • Peer Reviewed / Open Access
• [Journal Article] Interleukin 27 inhibits atherosclerosis via immunoregulation of macrophages in mice. (2013)
  • Author(s): Hirase T, Hara H, Miyazaki Y, Ide N, Nishimoto-Hazuku A, Fujimoto H, Saris CJM, Yoshida H, Node K
  • Journal Title: Am. J. Physiol. Heart Circ. Physiol. Volume: 305 Issue: 3 Pages: H420-H429
  • DOI: 10.1152/ajpheart.00198.2013
  • Peer Reviewed
• [Journal Article] Egr-2 transcription factor is required for Blimp-1 mediated IL-10 production in IL-27 stimulated CD4(+) T cells (2013)
  • Author(s): Iwasaki, Y.
  • Journal Title: Eur J Immunol Volume: undefined Issue: 4 Pages: 1063-73
  • DOI: 10.1002/eji.201242942
  • Peer Reviewed
• [Journal Article] Local apoptosis modulates early mammalian brain development through the elimination of morphogen producing cells. (2013)
  • Author(s): Nonomura, K., Yamaguchi, Y., Hamachi, M., Koike, M., Uchiyama, Y., Nakazato, K., Mochizuki, A., Sakaue-Sawano, A., Miyawaki, A., Yoshida, H., Kuida, K., and Miura, M.
  • Journal Title: Dev. Cell Volume: 27 Issue: 6 Pages: 621-634
  • DOI: 10.1016/j.devcel.2013.11.015
  • Peer Reviewed
• [Journal Article] トリパノソーマ感染防御におけるIL-17の役割 (2013)
  • Author(s): 吉田裕樹
  • Journal Title: 臨床免疫・アレルギー科 Volume: 60 Pages: 340-345
  • NAID: 40019808162
• [Journal Article] 動脈硬化と慢性炎症 (2013)
  • Author(s): 吉田裕樹、平瀬徹明
  • Journal Title: Vascular Medicine Volume: 9 Pages: 187-191
• [Presentation] Phospholipids bind to siglec-9 and induce immunosuppressive effect against LPS stimulation (2015)
  • Author(s): Miyake, Yasunobu Yamasaki, Sho Yoshida, H
  • Organizer: The 44th annual meeting of the Japanese Society for Immunology
  • Place of Presentation: 札幌
  • Year and Date: 2015-11-18
• [Presentation] IL-27-producing CD4+ T cells induced during malaria infection are distinct from Tr1 cells. (2015)
  • Author(s): Kimura, D Miyakoda, M Doe, Henrietta Terko Kimura, K Hara, H Yoshida, H Yui, K
  • Organizer: The 44th annual meeting of the Japanese Society for Immunology
  • Place of Presentation: 札幌
  • Year and Date: 2015-11-18
• [Presentation] Yasunobu Miyake Sho Yamasaki Hiroki, Yoshida (2015)
  • Author(s): Yasunobu Miyake Sho Yamasaki Hiroki, Yoshida
  • Organizer: Cytokines Congres 2015 (3rd Anual Meeting of the International Cytokine and Interferon Society)
  • Place of Presentation: Bamberg, Germany
  • Year and Date: 2015-10-11
  • Int'l Joint Research
• [Presentation] 結核菌認識受容体Mincleの安定化を担う分子MCL (2015)
  • Author(s): 三宅靖延 山崎晶 吉田裕樹
  • Organizer: 結核菌認識受容体Mincleの安定化を担う分子MCL
  • Place of Presentation: 東京
  • Year and Date: 2015-07-17
• [Presentation] Entamoebaにおけるシスト形成の制御機構の解明 (2015)
  • Author(s): 見市文香 宮本智文 高尾省子 Jeelani Ghulam 野崎知義 原博満 吉田裕樹
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 東京
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] マラリア原虫特異的CD4+T細胞が産生するIL-27は他のCD4+T細胞の防御機能を抑制する (2015)
  • Author(s): 木村大輔 都田真奈 木村一美 本間季里 吉田裕樹 由井克之
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 東京
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] Activation of innate immunity mediated by the IgSFR2/CARD9 pathway is involved in severe influenza pneumonia (2014)
  • Author(s): Uematsu T, Iizasa E, Kobayashi N, Yoshida H, Hara H
  • Organizer: The 43rd annual meeting of the Japanese Society for Immunology
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Innate recognition of mycolic acid-containing lipids in mycobacteria. (2014)
  • Author(s): Iizasa E, Uematsu T, Kubota M, Kiyohara H, Chuma Y, Matsuzak, G, Yamasaki S, Yoshida H, Hara H
  • Organizer: The 43rd annual meeting of the Japanese Society for Immunology
  • Place of Presentation: kyoto, Japan
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] IL-27-producing malaria-specific CD4+ T cells regulate protective immune responses. (2014)
  • Author(s): Kimura D, Miyakoda M, Kimura K, Honma K, Hara H, Yoshida H, Yui K
  • Organizer: The 43rd annual meeting of the Japanese Society for Immunology
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Mycobacterium tuberculosis-derived mycolic acid shows an adjuvant activity by activation of the ITAM receptor/CARD9-mediated innate immunity. (2014)
  • Author(s): Kubota M, Iizasa E, Kiyohara H, Chuma Y, Hara H, Yoshida H
  • Organizer: 2nd Anual Meeting of the International Cytokine and Interferon Society
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2014-10-26 – 2014-10-29
• [Presentation] 赤痢アメーバのシスト形成を制御するコレステロール硫酸の解析 (2014)
  • Author(s): 見市文香, 宮本智文, Ghulam J, 原博満, 野崎智義, 吉田裕樹
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] 結核菌細胞壁のミコール酸含有脂質を認識する新規自然免疫受容体 (2014)
  • 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67回日本細菌学会九州支部会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-09-05 – 2014-09-06
• [Presentation] インフルエンザウイルス感染における ITAM 関連受容体-CARD9シグナルを介した新規自然免疫活性化経路の解析. (2014)
  • Author(s): 植松崇之, 飯笹英一, 小林憲忠, 吉田裕樹, 原博満
  • Organizer: 第51回日本ウイルス学会九州支部総会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-09-05 – 2014-09-06
• [Presentation] IgSFR2は結核菌細胞壁のミコール酸含有脂質を認識する自然免疫受容体である. (2014)
  • Author(s): 飯笹英一, 植松崇之, 杉田昌彦, 山崎晶, 吉田裕樹, 原博満
  • Organizer: 第79回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2014-06-19 – 2014-06-20
• [Presentation] 赤痢アメーバのシスト形成を制御するコレステロール硫酸の解析 (2014)
  • Author(s): 見市文香, 宮本智文, Ghulam J, 原博満, 野崎智義, 吉田裕樹
  • Organizer: 第56回 日本脂質生化学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-06-06 – 2014-06-07
• [Presentation] マラリア原虫特異的CD4+T細胞は、IL-27を介してCD4+T細胞の防御機能を抑制する (2014)
  • Author(s): 木村大輔, 都田真奈, 木村和美, 本間季里, 堀昌平, 吉田裕樹, 由井克之
  • Organizer: 第83回日本寄生虫学会大会
  • Place of Presentation: 愛媛
• [Presentation] 赤痢アメーバ"マイトソーム"が産生するコレステロール硫酸の機能解析 (2014)
  • Author(s): 見市文香, 宮本智文, J. Ghulam, 原博満, 野崎知義, 吉田裕樹
  • Organizer: 第83回日本寄生虫学会大会
  • Place of Presentation: 愛媛
• [Presentation] Interleukin 27 inhibits hepatic steatosis induced by high fat diet in mice. (2013)
  • Author(s): Hirase T, Fujimoto H, Hiromitsu H, Yoshida H, Node K
  • Organizer: Cell Symposia; Immunometabolism: from Mechanisms to Therapy.
  • Place of Presentation: Toronto, Canada
• [Presentation] IL-27 affects helper T cell responses via regulation of PGE2 production by macrophages. (2013)
  • Author(s): Sato Y, Hara H, Suzuki S, Kaisho T, Yoshida H
  • Organizer: 15th International Congress of Immunology
  • Place of Presentation: Milan, Italy
• [Presentation] Identification of novel innate pattern recoginition receptors for mycobacterium tuberculosis. (2013)
  • Author(s): Iizasa E, Miyamoto T, Uematsu T, Ishikawa T, Yamasaki S, Matsuzaki G, Yoshida H, Hara H
  • Organizer: 15th International Congress of Immunology
  • Place of Presentation: Milan, Italy
• [Presentation] Essential role of ITAM-Syk-IL-1 axis in skin dendritic cells for the sensitization of allergic contact dermatitis. (2013)
  • Author(s): Hara H, Yasukawa S, Yoshida H, Furue M
  • Organizer: 15th International Congress of Immunology
  • Place of Presentation: Milan, Italy
• [Presentation] IL-27 affects helper T cell response via regulation of PGE2 production by macrophages. (2013)
  • Author(s): Sato Y, Hara H, Suzuki S, Kaisho T, Yoshida H
  • Organizer: Inaugural meeting of the international cytokine and interferon society (ICIS).
  • Place of Presentation: Milan, Italy
• [Presentation] Interleukin 27 inhibits atherosclerosis via immunoregulation of macrophages in mice. (2013)
  • Author(s): Yoshida H, Hirase T, Hara H, Node K
  • Organizer: Autoimmunity Congress Asia
  • Place of Presentation: Hong Kong, China
• [Presentation] Activation of innate immunity through the CARD9 pathway is involved in severe influenza pneumonia. (2013)
  • Author(s): Uematsu T, Iizasa E, Kobayashi N, Yoshida H, Hara H
  • Organizer: 15th International Congress of Immunology
  • Place of Presentation: Milan, Italy
• [Presentation] IL-1 released by skn dendritic cells activated through Syk and CARD9 pathway is essential for the sensitization of allergic contact dermatitis. (2013)
  • Author(s): Hara H, Yasukawa S, Furue M, Yoshida H
  • Organizer: IMMUNOLOGY 2013 AAI Annual Meeting
  • Place of Presentation: Hawaii, USA
• [Presentation] IL-27 afects helper t cell response via reguation of PGE2 production by macrophages. (2013)
  • Author(s): Sato Y, Hara H, Suzuki S, Kaisho T, Yoshida H
  • Organizer: The joint international meeting of the 78th meeting of the Japanese societyt of interferon and cytokine research + the 21st international symposium on molecular cell biology of macrophages.
  • Place of Presentation: 東京
• [Presentation] Identification and analysis of two novel pattern recoginition receptors for Mycobacterium tuberculosis. (2013)
  • Author(s): Iizasa E, Miyamoto T, Uematsu T, Ishikawa T, Yamasaki S, Yoshida H, Hara H
  • Organizer: The joint international meeting of the 78th meeting of the Japanese societyt of interferon and cytokine research + the 21st international symposium on molecular cell biology of macrophages.
  • Place of Presentation: 東京
• [Presentation] Exacervation of delayed-type hypersensitivity responses in mice with T cell-specific deletion of Apaf1. (2013)
  • Author(s): Tong H, Iizasa E, Hara H, Yoshida H
  • Organizer: 第42回日本免疫学会学術集会.
  • Place of Presentation: 幕張
• [Presentation] Adjuvant activity of Mycobacterium tubeculosis-derived mycolic acid through activation of the ITAM receptor/CARD9-mediated innate immunity. (2013)
  • Author(s): Kubota M, Iizasa E, Kiyohara H, Nakama Y, Hara H, Yoshida H
  • Organizer: 第42回日本免疫学会学術集会.
  • Place of Presentation: 幕張
• [Presentation] Il-27 is produced by CD4+ T cells during infection with malaria parasites and inhibits protective immune responses. (2013)
  • Author(s): Kimura D, Miyakoda M, Kimura K, Honma K, Hara H, Hori S, Yoshida H, Yui K
  • Organizer: 第42回日本免疫学会学術集会.
  • Place of Presentation: 幕張
• [Presentation] Identification of an ITAM-coupled pattern recognition receptor that recognizes the mycobacterial cell wall compontent mycolic acids. (2013)
  • Author(s): Iizasa E, Uematsu T, Matuzaki G, Yamasaki S, Yoshida H, Hara H
  • Organizer: 第42回日本免疫学会学術集会.
  • Place of Presentation: 幕張
• [Presentation] Analysis for the role of Syk-CARD9-regulated IL-1 secretion pathway in DCs in contact hypersensitivity by the mixed-chimera diphtheria toxin receptor (DTR)-mediated conditional cell knockout (MixC-Treck) method, a novel method for conditional gene targeting in mice. (2013)
  • Author(s): Hara H, Yasukawa S, Natsuaki Y, Kabashima K, Furue M, Yoshida H
  • Organizer: 第42回日本免疫学会学術集会.
  • Place of Presentation: 幕張
• [Presentation] 赤痢アメーバ“マイトソーム”の硫酸活性化経路の生化学的解析 (2013)
  • Author(s): 見市文香, 宮本智文, 原博満, 野崎智義, 吉田裕樹
  • Organizer: 第86回日本生化学会大会,日本、横浜
  • Place of Presentation: 横浜
• [Remarks] 佐賀大学医学部免疫学教室
  • URL: http://mcis-sagamed.info/