New role of interleukin-17 in protective immunity against intracellular bacterial infections and its application

• Project/Area Number: 21390132
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: University of the Ryukyus
• Principal Investigator: MATSUZAKI Goro 琉球大学, 熱帯生物圏研究センター, 教授 (30229455)
• Co-Investigator(Kenkyū-buntansha): UMEMURA Masayuki 琉球大学, 熱帯生物圏研究センター, 助教 (90359985) ; ARAKAWA Takeshi 琉球大学, 熱帯生物圏研究センター, 准教授 (50305190)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2011: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2010: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2009: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
• Keywords: 感染免疫 / インターロイキン17 / 細胞内寄生性細菌 / 感染防御 / 結核菌 / 腫瘍 / インターロイキンー17 / BCG / リステリア菌 / ネズミチフス菌 / インターロイキン-17A / T細胞レセプターγδT細胞 / マイコバクテリア感染 / リステリア菌感染

Research Abstract

IL-17 was identified as a proinflammatory cytokine which induce generation and migration of neutrophils. We demonstrated that IL-17 also participate in protective immunity against intracellular bacterial infection in neutrophil-independent manner. To address the mechanism of IL-17-mediated protection, IL-17-deficient mice infected with mycobacteria were analyzed. In the absence of IL-17 produced byγδT cells, mature granuloma formation in the lung was impaired, with attenuated protective immunity against Mycobacterium tuberculosis. Induction of adhesion molecules by IL-17 was indicated to be important in the mature granuloma formation. All the results suggest that regulation of IL-17-producing cells would be a new approach to enhance protective immunity against tuberculosis.

Research Products

• [Journal Article] Merozoite surface protein-1 of Plasmodium yoelii fused via an oligosaccharide moiety of cholera toxin B subunit glycoprotein expressed in yeast induced protective immunity against lethal malaria infection in mice (2012)
  • Author(s): Miyata T., Harakuni, T., Taira, T., Matsuzaki, G., Arakawa, T.
  • Journal Title: Vaccine Volume: 30 Pages: 948-958
  • Peer Reviewed
• [Journal Article] Interleukin-17A is involved in enhancement of tumor progression in murine intestine (2012)
  • Author(s): Oshiro, K., Kohama, K., Umemura, M., Uyttenhove, C., Inagaki-Ohara, K., Arakawa, T, Harada, H., Nakae, S., Iwakura, Y., Nishimaki, T., Matsuzaki, G.
  • Journal Title: Immunobiology Volume: 217(1) Pages: 54-60
  • Peer Reviewed
• [Journal Article] Tricomponent immunopotentiating system as a novel molecular design strategy for malaria vaccine development (2011)
  • Author(s): Miyata, T., Harakuni, T., Tsuboi, T., Aattabongkot, J., Ikehara, A., Tacibana, M., Torii, M., Matsuzaki, G., Arakawa, T.
  • Journal Title: Infect. Immune Volume: 79 Pages: 4260-4275
  • Peer Reviewed
• [Journal Article] Contribution of IL-17-producingγδT cells to the efficacy of anticancer chemotherapy (2011)
  • Author(s): Ma, Y., Aymeric L., Locher, C., Mattarollo, S. R, Delahaye, N., F., Pereira, P., Boucontet, L., Apetoh, L., Ghironghelli, F., Casares, N., Lasarte, J. J., Matsuzaki, G., Ikuta, K., Ryffel, B., Benlagha, K., Tensiere, A., Ibrahim, N., Dechanet-Merville, ., Chaput, N., Smyth, M. J., Kroemer, G., Zitvoge, L.
  • Journal Title: J. Exp. Med Volume: 208 Pages: 491-503
  • Peer Reviewed
• [Journal Article] Interleukin-17A is involved in enhancement of tumor progression in murine intestine (2011)
  • Author(s): K.Oshiro
  • Journal Title: Immunobiology Volume: 217 Issue: 1 Pages: 54-60
  • DOI: 10.1016/j.imbio.2011.08.002
  • Peer Reviewed
• [Journal Article] Merozoite surface protein-1 of Plasmodium yoelii fused via an oligosaccharidemoiety of cholera toxin B subunit glycoprotein expressed in yeast induced protective immunity against lethal malaria infection in mice (2011)
  • Author(s): T.Miyata
  • Journal Title: Vaccine Volume: 30 Issue: 5 Pages: 948-958
  • DOI: 10.1016/j.vaccine.2011.11.059
  • Peer Reviewed
• [Journal Article] Tricomponent immunopotentiating system as a novel molecular design strategy for malaria vaccine development (2011)
  • Author(s): T.Miyata
  • Journal Title: Infect.Immun. Volume: 79 Issue: 10 Pages: 4260-4275
  • DOI: 10.1128/iai.05214-11
  • Peer Reviewed
• [Journal Article] Contribution of IL-17-producing γ δ T cells to the efficacy of anticancer chemotherapy. (2011)
  • Author(s): Y.Ma, et al.
  • Journal Title: Journal of Experimental Medicine Volume: 208 Pages: 491-503
  • Peer Reviewed
• [Journal Article] Interleukin-17A is required to suppress invasion of Salmonella enterica serovar Typhimurium to enteric mucosa (2010)
  • Author(s): Mayuzumi, H., Inagaki-Ohara, K., Uyttenhove, C., Okamoto, Y., Matsuzaki, G.
  • Journal Title: Immunology Volume: 131(3) Pages: 377-385
  • Peer Reviewed
• [Journal Article] Plasmodium vivax ookinete surface protein Pvs25 linked to cholera toxin B subunit induces potent transmission-blocking immunity by intranasal as well as subcutaneous immunization (2010)
  • Author(s): Miyata, T., T. Harakuni, T. Tsuboi, J. Sattabongkot, H. Kohama, M. Tachibana, G. Matsuzaki, M. Torii, and T Arakawa
  • Journal Title: Infect. Immun Volume: 78 Pages: 3773-3782
  • Peer Reviewed
• [Journal Article] Essential role of interleukin-17A in the formation of a mycobacterial infection-induced granuloma in the lung (2010)
  • Author(s): Okamoto, Y. Y., Umemura, M., Yahagi, A., O' Brien, R. L. Ikuta, K, Kishihara, K., Hara, H., Nakae, S., Iwakura, Y. and Matsuzaki, G.
  • Journal Title: J. Immunol Volume: 184(8) Pages: 4414-4422
  • Peer Reviewed
• [Journal Article] Suppressed induction of mycobacterial antigen-specific Th1-type CD4^+T cells in the lung after pulmonary mycobacterial infection (2010)
  • Author(s): Yahagi, A. Umemura, M., Tamura, T., Kariyone, A., Begum, M. D., Kawakami, K., Okamoto, Y., Hamada, S., Oshiro, K., Kohama, H., Arakawa, T., Ohara, N., Takatsu, K. and Matsuzaki, G.
  • Journal Title: Int. Immunol Volume: 22(4) Pages: 307-318
  • Peer Reviewed
• [Journal Article] Suppressed I, nduction of mycobacterial antigen-specific Th1-type CD4+ T cells in the lung after pulmonary mycobacterial infection. (2010)
  • Author(s): A.Yahagi, et al.
  • Journal Title: International Immunology Volume: 22 Pages: 307-318
  • Peer Reviewed
• [Journal Article] Essential role of interleukin-17A in the formation of a mycobacterial infection-induced granuloma in the lung. (2010)
  • Author(s): Y.Y.Okamoto, et al.
  • Journal Title: Journal of Immunology Volume: 184 Pages: 4414-4422
  • Peer Reviewed
• [Journal Article] Interleukin-17A is required to suppress invasion of Salmonella enterica serovar Typhimurium to enteric mucosa. (2010)
  • Author(s): H.Mayuzumi, et al.
  • Journal Title: Immunology Volume: 131 Pages: 377-385
  • Peer Reviewed
• [Journal Article] Accelerated induction of mycobacterial antigen-specific CD8^+T cells in the Mycobacterium tuberculosis-infected lung by subcutaneous vaccination with Mycobacterium bovis bacilli Calmette et Guerin (2009)
  • Author(s): Begum, M. D., Umemura, M., Yahagi, A., Okamoto, Y., Hamada, S., Ohshiro, K., and Matsuzaki, G.
  • Journal Title: Immunology Volume: 128 Pages: 556-563
  • Peer Reviewed
• [Journal Article] Accelerated induction of mycobacterial antigen-specific CD8^+ T cells in the Myco bacterium tuberculosis-infected lung by subcutaneous vaccination with Mycobacterium bovis bacilli Calmette et Guerin (2009)
  • Author(s): Begum, M.D.
  • Journal Title: Immunology 128 Pages: 556-563
  • Peer Reviewed
• [Presentation] Regulation of immune response against Mycobacterium infection by IL-17-producing gamma/delta T cells (2012)
  • Author(s): G.Matsuzaki
  • Organizer: 第85回日本細菌学会総会
  • Place of Presentation: 長崎県長崎市(招待講演)
  • Year and Date: 2012-03-28
• [Presentation] 慢性結核感染におけるインターロイキン-17の役割 (2012)
  • Author(s): 當山清吾
  • Organizer: 第85回日本細菌学会総会
  • Place of Presentation: 長崎県長崎市
  • Year and Date: 2012-03-27
• [Presentation] 慢性結核感染におけるインターロイキン-17の役割 (2012)
  • Author(s): 當山清吾、梅村正幸、芳田裕子、矢作綾野、安田直子、中江進、岩倉洋一郎、松崎吾朗
  • Organizer: 第85回日本細菌学会総会
  • Place of Presentation: 長崎
• [Presentation] Regulation of immune response against Mycobacterium infection by IL-17-producing gamma/delta T cells. (2012)
  • Author(s): Matsuzaki, G., Umemura M.
  • Organizer: 第85回日本細菌学会総会
  • Place of Presentation: 長崎
• [Presentation] 結核菌感染におけるIL-17AおよびIL-17Fの役割 (2011)
  • Author(s): 梅村正幸
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 千葉県千葉市
  • Year and Date: 2011-11-28
• [Presentation] Interkeukin-17による免疫制御と感染防御 (2011)
  • Author(s): 松崎吾朗
  • Organizer: 第63回日本皮膚科学会西部支部学術大会
  • Place of Presentation: 沖縄県宜野湾市(招待講演)
  • Year and Date: 2011-10-08
• [Presentation] Role of IL-17-producing gamma/delta T cells in granuloma for mation of mycobacteria-infected lung (2011)
  • Author(s): G.Matsuzaki
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: 北海道札幌市(招待講演)
  • Year and Date: 2011-09-08
• [Presentation] 結核菌慢性感染におけるIL-17ファミリーの防御能 (2011)
  • Author(s): 梅村正幸
  • Organizer: 第64回日本細菌学会九州支部総会
  • Place of Presentation: 福岡県北九州市
  • Year and Date: 2011-08-26
• [Presentation] 結核菌に対する感染防御におけるIL-17ファミリーの役割 (2011)
  • Author(s): 梅村正幸
  • Organizer: 第22回日本生体防御学会学術総会
  • Place of Presentation: 沖縄県那覇市
  • Year and Date: 2011-06-30
• [Presentation] 結核菌感染におけるIL-17AおよびIL-17Fの役割 (2011)
  • Author(s): 梅村正幸、當山清吾、中江進、岩倉洋一郎、松崎吾朗
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 千葉
• [Presentation] Role of IL-17-producing gamma/delta T cells in granuloma formation of mycobacteria-infected lung (2011)
  • Author(s): Matsuzaki, G., Okamoto Yoshida, Y., Umemura, M.
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: Sapporo
• [Presentation] Essential role of interleukin-17A in the formation of a mycobacterial infection-induced granuloma in the lung (2011)
  • Author(s): Umemura M, Okamoto Y, Yahagi A, Toma N, Nakae S, Iwakura Y, Matsuzaki G.
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: Sapporo
• [Presentation] 結核菌に対する感染防御におけるIL-17ファミリーの役割 (2011)
  • Author(s): 梅村正幸、當山清悟、岡本祐子、矢作綾野、當眞奈海、中江進、岩倉洋一郎、松崎吾朗
  • Organizer: 第22回日本生体防御学会学術総会
  • Place of Presentation: 那覇
• [Presentation] Essential role of interleukin-17A in the formation of mycobacterial infection-induced granuloma in the lung (2010)
  • Author(s): Umemura M, Yoshida YO, Yahagi A, Nakane S, Iwakura Y, Matsuzaki G
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe
• [Presentation] Suppressed induction of mycobacterial antigen-specific Th1-type CD4+T cells in the lung after pulmonary mycobacterial infection (2010)
  • Author(s): Yahagi a, Umemura M, Tamura T, Kariyone A, Begum DM, Yoshida, YO, Ishihara K, Takatsu K, Matsuzaki G
  • Organizer: 14^<th> Inteernational Congress of Immunology
  • Place of Presentation: Kobe
• [Presentation] マイコバクテリア感染肺におけるIL-17A依存性肉芽腫形成メカニズムの解析 (2010)
  • Author(s): 梅村正幸、岡本祐子、矢作綾野、本田尚子、當眞奈海、中江進、岩倉洋一郎、松崎吾朗
  • Organizer: 第21回日本生体防御学会学術総会
  • Place of Presentation: 仙台
• [Presentation] 三部構成免疫賦活システム(TIPs) (2010)
  • Author(s): 宮田健、原國哲也、池原歩、坪井敬文、J. Sattabongkot、橘真由美、鳥居本美、松崎吾朗、新川武
  • Organizer: 第21回日本生体防御学会学術総会
  • Place of Presentation: 仙台
• [Presentation] 結核菌肺感染に対する防御免疫におけるインターロイキン-17A(IL-17A)の役割 (2010)
  • Author(s): 松崎吾朗, 岡本祐子, 梅村正幸
  • Organizer: 第85回日本結核病学会総会
  • Place of Presentation: 京都
• [Presentation] 結核菌肺感染に対する防御免疫におけるインターロイキン-17A(IL-17A)の役割 (2010)
  • Author(s): 松崎吾朗, 他
  • Organizer: 第85回日本結核病学会総会
  • Place of Presentation: 京都テルサ(京都)
• [Presentation] 結核菌感染肺におけるIL-17A産生T細胞の防御機構の解明 (2009)
  • Author(s): 岡本裕子
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-03
• [Presentation] 結核菌感染した肺における防御免疫誘導の制御機構 (2009)
  • Author(s): 松崎吾朗、矢作綾野、Dilara Mst. Begum、梅村正幸
  • Organizer: 第50回日本熱帯医学会シンポジウム7「結核と腸管感染症の新知見」
  • Place of Presentation: 沖縄
  • Year and Date: 2009-10-23
• [Presentation] 肺におけるマイコバクテリア抗原特異的Th1型免疫応答制御への肺内CD11c+細胞の関与の検討 (2009)
  • Author(s): 矢作綾野、梅村正幸、田村敏生、D. M. Begum、岡本裕子、新城紀久子、刈米アイ、高津聖志、松崎吾朗
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪
• [Presentation] 結核菌感染肺におけるIL-17A産生T細胞の防御機構の解明 (2009)
  • Author(s): 岡本裕子、梅村正幸、矢作綾野、中江進、岩倉洋一郎、松崎吾朗
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪
• [Presentation] Mycobacterium tuberculosis感染に対するIL-17産生T細胞の防御機構の解明 (2009)
  • Author(s): 岡本裕子、梅村正幸、矢作綾野、中江進、岩倉洋一郎、松崎吾朗
  • Organizer: 第20回日本生体防御学会学術総会
  • Place of Presentation: 東京
• [Presentation] Mycobacterium tuberculosis(Mtb)感染肺へのMtb抗原特異的CD8+T細胞誘導に対するBCG接種の効果の検討 (2009)
  • Author(s): 矢作綾野、D. M. Begum、梅村正幸、岡本裕子、松崎吾朗
  • Organizer: 第20回日本生体防御学会学術総会
  • Place of Presentation: 東京
• [Remarks]
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