Anti-fungal Immunity

• Project/Area Number: 26293094
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: Chiba University
• Principal Investigator: Saijo Shinobu 千葉大学, 真菌医学研究センター, 准教授 (60396877)
• Co-Investigator(Kenkyū-buntansha): 岩倉 洋一郎 東京理科大学, 付置研究所, 教授 (10089120) ; 米山 光俊 千葉大学, 真菌医学研究センター, 教授 (40260335)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000); Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2015: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
• Keywords: C-type lectin / 遺伝子改変動物 / サイトカイン / C型レクチン / 真菌感染 / 感染防御 / レクチン

Outline of Final Research Achievements

Myeloid cells act central roles in inflammatory responses. C-type lectin receptors (CLRs) are key players that are expressed mainly in these cells to orchestrate immune responses for maintaining immune homeostasis. These receptors recognize carbohydrate structures in microbes, including fungi, bacteria, viruses, and parasites, as pathogen-associated molecular patterns (PAMPs). Owing to the activities, the pleiotropic roles of CLRs has been suggested to have an important effect on homeostasis in the body. In this study, we found that collaboration of several C-type lectins are important in anti-fungal immunity.

Research Products

• [Journal Article] Dectin-1 Plays an Important Role in House Dust Mite-Induced Allergic Airway Inflammation through the Activation of CD11b+ Dendritic Cells. (2017)
  • Author(s): Ito T, Hirose K, Norimoto A, Tamachi T, Yokota M, Saku A, Takatori H, Saijo S, Iwakura Y, Nakajima H.
  • Journal Title: J Immunol. Volume: 198 Issue: 1 Pages: 61-70
  • DOI: 10.4049/jimmunol.1502393
  • Peer Reviewed
• [Journal Article] Dectin-2-dependent host defense in mice infected with serotype 3 Streptococcus pneumoniae (2016)
  • Author(s): Akahori Y, Miyasaka T, Toyama M, Matsumoto I, Miyahara A, Zong T, Ishii K, Kinjo Y, Miyazaki Y, Saijo S, Iwakura Y, Kawakami K.
  • Journal Title: BMC Immunol Volume: 17 Issue: 1 Pages: 1-1
  • DOI: 10.1186/s12865-015-0139-3
  • Peer Reviewed / Open Access
• [Journal Article] Dectin-1 and Dectin-2 promote control of the fungal pathogen Trichophyton rubrum independently of IL-17 and adaptive immunity in experimental deep dermatophytosis (2016)
  • Author(s): Fabio Yoshikawa, Rikio Yabe, Yoichiro Iwakura, Sandro Rogerio de Almeida, Shinobu Saijo
  • Journal Title: Innate Immunity Volume: in press Issue: 5 Pages: 316-24
  • DOI: 10.1177/1753425916645392
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Phosphoinositide 3-Kinase δ Regulates Dectin-2 Signaling and the Generation of Th2 and Th17 Immunity. (2016)
  • Author(s): Lee MJ, Yoshimoto E, Saijo S, Iwakura Y, Lin X, Katz HR, Kanaoka Y, Barrett NA.
  • Journal Title: J Immunol. Volume: 197 Issue: 1 Pages: 278-87
  • DOI: 10.4049/jimmunol.1502485
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Dectin-2 Recognizes Mannosylated O-antigens of Human Opportunistic Pathogens and Augments Lipopolysaccharide Activation of Myeloid Cells. (2016)
  • Author(s): Wittmann A, Lamprinaki D, Bowles KM, Katzenellenbogen E, Knirel YA, Whitfield C, Nishimura T, Matsumoto N, Yamamoto K, Iwakura Y, Saijo S, Kawasaki N.
  • Journal Title: J Biol Chem. Volume: 291 Issue: 34 Pages: 17629-38
  • DOI: 10.1074/jbc.m116.741256
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The innate immune receptor Dectin-2 mediates the phagocytosis of cancer cells by Kupffer cells for the suppression of liver metastasis. (2016)
  • Author(s): Kimura Y., Inoue A.., Hangai S.., Saijo S., Negishi H., Nishio J., Yamasaki S., Iwakura Y., Yanai H., Taniguchi T.
  • Journal Title: Proc. Natl. Acad. Sci. U S A. Volume: 113 Issue: 49 Pages: 14097-14102
  • DOI: 10.1073/pnas.1617903113
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A critical role of Dectin-1 in hypersensitivity pneumonitis (2015)
  • Author(s): Higashino-Kameda M, Yabe-Wada T, Matsuba S, Takeda K, Anzawa K, Mochizuki T, Makimura K, Saijo S, Iwakura Y, Toga H, Nakamura A
  • Journal Title: Inflamm Res Volume: 65 Issue: 3 Pages: 235-44
  • DOI: 10.1007/s00011-015-0910-1
  • Peer Reviewed / Open Access
• [Journal Article] CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis. (2015)
  • Author(s): Murayama A.M, Kakuta S, Inoue A, Umeda N, Yonezawa T, Maruhashi T, Tateishi K, Ishigame H, Yabe R, Ikeda S, Seno A, Chi H-H, Hashiguchi Y, Kurata R, Tada T, Kubo S, Sato N, Liu Y, Hattori M, Saijo S, Matsushita M, Fujita T, Sumida T, Iwakura Y
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 1-12
  • DOI: 10.1038/ncomms9483
  • NAID: 120006986869
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 1.Inhibition of Dectin-1 signaling ameliorates colitis by inducing Lactobacillus- mediated regulatory T cell expansion in the intestine. (2015)
  • Author(s): Ce Tang, Tomonori Kamiya, Yang Liu, Motohiko Kadoki, Shigeru Kakuta, Kenshiro Oshima, Masahira Hattori, Kozue Takeshita, Takanori Kanai, Shinobu Saijo and Yoichiro Iwakura
  • Journal Title: Cell Host & Microbe Volume: 18 Issue: 2 Pages: 183-197
  • DOI: 10.1016/j.chom.2015.07.003
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2(+)Vγ6(+)γδ T cells. (2015)
  • Author(s): Akitsu A, Ishigame H, Kakuta S, Chung SH, Ikeda S, Shimizu K, Kubo S, Liu Y, Umemura M, Matsuzaki G, Yoshikai Y, Saijo S, Iwakura Y.
  • Journal Title: Nat Commun Volume: 6 Issue: 1 Pages: 7464-7464
  • DOI: 10.1038/ncomms8464
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice. (2015)
  • Author(s): Uryu H, Hashimoto D, Kato K, Hayase E, Matsuoka S, Ogasawara R, Takahashi S, Maeda Y, Iwasaki H, Miyamoto T, Saijo S, Iwakura Y, Hill GR, Akashi K, Teshima T.:
  • Journal Title: Blood Volume: 125 Issue: 19 Pages: 3014-23
  • DOI: 10.1182/blood-2014-12-615781
  • Peer Reviewed / Open Access
• [Journal Article] α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice. (2015)
  • Author(s): Uryu H, Hashimoto D, Kato K, Hayase E, Matsuoka S, Ogasawara R, Takahashi S, Maeda Y, Iwasaki H, Miyamoto T, Saijo S, Iwakura Y, Hill GR, Akashi K, Teshima T.
  • Journal Title: blood Volume: in press
  • Peer Reviewed
• [Journal Article] Phagocytosis-dependent activation of a TLR9-BTK-calcineurin-NFAT pathway co-ordinates innate immunity to Aspergillus fumigatus. (2015)
  • Author(s): Herbst S, Shah A, Mazon Moya M, Marzola V, Jensen B, Reed A, Birrell MA, Saijo S, Mostowy S, Shaunak S, Armstrong-James D.
  • Journal Title: EMBO Mol Med. Volume: 7 Issue: 3 Pages: 240-258
  • DOI: 10.15252/emmm.201404556
  • Peer Reviewed
• [Journal Article] Dectin-2 deficiency promotes Th2 response and mucin production in the lungs after pulmonary infection with Cryptococcus neoformans. (2015)
  • Author(s): Nakamura Y, Sato K, Yamamoto H, Matsumura K, Matsumoto I, Nomura T, Miyasaka T, Ishii K, Kanno E, Tachi M, Yamasaki S, Saijo S, Iwakura Y, Kawakami K.
  • Journal Title: Infect Immun. Volume: 83 Issue: 2 Pages: 671-681
  • DOI: 10.1128/iai.02835-14
  • Peer Reviewed
• [Journal Article] The pH-responsive PacC transcription factor of Aspergillus fumigatus governs epithelial entry and tissue invasion during pulmonary aspergillosis. (2014)
  • Author(s): Bertuzzi M, Schrettl M, Alcazar-Fuoli L, Cairns TC, Munoz A, Walker LA, Herbst S, Safari M, Cheverton AM, Chen D, Liu H, Saijo S, Fedorova ND, Armstrong-James D, Munro CA, Read ND, Filler SG, Espeso EA, Nierman WC, Haas H, Bignell EM.
  • Journal Title: PLoS Pathog. Volume: 10 Issue: 10 Pages: e1004413-e1004413
  • DOI: 10.1371/journal.ppat.1004413
  • Peer Reviewed
• [Journal Article] Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria. (2014)
  • Author(s): Yonekawa A, Saijo S, Hoshino Y, Miyake Y, Ishikawa E, Suzukawa M, Inoue H, Tanaka M, Yoneyama M, Oh-Hora M, Akashi K, Yamasaki S.
  • Journal Title: Immunity Volume: 41 Issue: 3 Pages: 402-13
  • DOI: 10.1016/j.immuni.2014.08.005
  • Peer Reviewed / Open Access
• [Journal Article] Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses. (2014)
  • Author(s): Chiba S, Ikushima H, Ueki H, Yanai H, Kimura Y, Hangai S, Nishio J, Negishi H, Tamura T, Saijo S, Iwakura Y, Taniguchi T.
  • Journal Title: eLife Volume: 04177 Pages: 04177-04177
  • DOI: 10.7554/elife.04177
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dectin-1 pathway activates robust autophagy-dependent unconventional protein secretion in human macrophages. (2014)
  • Author(s): Ohman T, Teirila L, Lahesmaa-Korpinen AM, Cypryk W, Veckman V, Saijo S, Wolff H, Hautaniemi S, Nyman TA, Matikainen S.
  • Journal Title: J Immunol. Volume: 192 Issue: 12 Pages: 5952-5962
  • DOI: 10.4049/jimmunol.1303213
  • Peer Reviewed
• [Journal Article] The role of C-type lectin receptors in host defense against microbial pathogens. (2014)
  • Author(s): Yabe R, Iwakura Y, Saijo S.
  • Journal Title: “Glycoscinece: Biology and Medicine” Volume: 1 Pages: 1-10
  • Peer Reviewed
• [Journal Article] Rag2-deficient IL-1 Receptor Antagonist-deficient Mice Are a Novel Colitis Model in Which Innate Lymphoid Cell-derived IL-17 Is Involved in the Pathogenesis. (2014)
  • Author(s): Akitsu A, Kakuta S, Saijo S, Iwakura Y.
  • Journal Title: Exp Anim. Volume: 63 Pages: 235-246
  • NAID: 130003391627
  • Peer Reviewed
• [Presentation] 真菌によるIL－17産生機構 (2016)
  • Author(s): 西城 忍
  • Organizer: AMED－CREST若手研究会
  • Place of Presentation: 大阪アカデミア （大阪府大阪市）
  • Year and Date: 2016-06-15
  • Invited
• [Presentation] 自然免疫による病原体防御の新展開 (2016)
  • Author(s): 西城 忍
  • Organizer: 第8回日本インターフェロン・サイトカイン学術集会
  • Place of Presentation: 長崎大学坂本キャンパス良準会館(長崎県長崎市）
  • Year and Date: 2016-05-13
  • Invited
• [Presentation] C型レクチンによる感染防御機構 (2015)
  • Author(s): 西城 忍
  • Organizer: 第34回日本糖質学会講演
  • Place of Presentation: 東京大学安田講堂(東京都文京区）
  • Year and Date: 2015-07-31
  • Invited
• [Presentation] 細菌・真菌の細胞壁構成成分とC型レクチン受容体による認識 (2015)
  • Author(s): 西城忍
  • Organizer: 第24回内毒素・LPS研究会
  • Place of Presentation: 東京大学農学部中島董一郎記念ホール（東京都文京区）
  • Year and Date: 2015-06-27
  • Invited
• [Presentation] 真菌感染防御機構におけるC型レクチンの役割 (2014)
  • Author(s): 西城忍
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都府京都市 京都国際会館
  • Year and Date: 2014-10-15 – 2014-10-18
  • Invited
• [Presentation] 真菌感染防御機構におけるC型レクチンの役割 (2014)
  • Author(s): 西城忍
  • Organizer: 第26回微生物シンポジウム
  • Place of Presentation: 東京都千代田区 都市センターホテル
  • Year and Date: 2014-09-19 – 2014-09-20
  • Invited
• [Book] C-type Lectin Receptors in Immunity (2016)
  • Author(s): Yabe, R., and S. Saijo
  • Total Pages: 215
  • Publisher: Springer
• [Remarks] 千葉大学真菌医学研究センター感染免疫分野
  • URL: http://cytokine.pf.chiba-u.jp/