Elucidation of novel innate immune system by analysis of host-parasite interaction

• Project/Area Number: 23689029
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: YAMAMOTO Masahiro 大阪大学, 微生物病研究所, 教授 (00444521)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥27,430,000 (Direct Cost: ¥21,100,000、Indirect Cost: ¥6,330,000); Fiscal Year 2013: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2012: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000); Fiscal Year 2011: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
• Keywords: インターフェロンγ / 自然免疫 / トキソプラズマ原虫 / 細胞自律的免疫系 / 自然免疫系 / ROP18 / ATF6β / 免疫系

Research Abstract

Interferon-g (IFN-g) is essential for host defense against intracellular pathogens. Stimulation of innate immune cells by IFN-g up-regulates ~2000 effector genes such as immunity-related GTPases including p65 guanylate-binding protein (GBP) family genes. We show that a cluster of GBP genes is required for host cellular immunity against the intracellular parasite Toxoplasma gondii. We generated mice deficient for all six GBP genes located on chromosome 3 by targeted chromosome engineering. Mice lacking Gbpchr3 were highly susceptible to T. gondii infection, resulting in increased parasite burden in immune organs. Furthermore, Gbpchr3-deleted macrophages were defective in IFN-g-mediated suppression of T. gondii intracellular growth. In addition, some members of Gbpchr3 restored the protective response against T. gondii in Gbpchr3-deleted cells. Thus, Gbpchr3 redundantly play a pivotal role in anti-T. gondii host defense by controlling IFN-g-mediated cellular innate immunity.

Research Products

• [Journal Article] Role of Mouse and Human Autophagy Proteins in IFN-γ-Induced Cell-Autonomous Responses against Thxoplasma gondii (2014)
  • Author(s): Jun Ohshima, Youngae Lee, Miwa Sasai, Tatsuya Saitoh, Ji Su Ma, Naganori Kamiyama, Yoshiharu Matsuura, Suh Pann-Ghill, Mikako Hayashi, Shigeyuki Ebisu, Kiyoshi Takeda, Shizuo Akira, and Masahiro Yamamoto.
  • Journal Title: The Journal of Immunology Volume: 192(7) Issue: 7 Pages: 3328-35
  • DOI: 10.4049/jimmunol.1302822
  • Peer Reviewed / Open Access
• [Journal Article] Guanylate binding proteins promote caspase-11-dependent pyroptosis in response to cytoplasmic LPS. (2014)
  • Author(s): Pilla DM, Hagar JA, Haldar AK, Mason AK, Degrandi D, Pfeffer K, Ernst RK, Yamamoto M, Miao EA, Coers J.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN-induced GTPases. (2014)
  • Author(s): Meunier E, Dick MS, Dreier RF, Schurmann N, Broz DK, Warming S, Roose-Girma M, Bumann D, Kayagaki N, Takeda K, Yamamoto M, Broz P.
  • Journal Title: Nature Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Role of the mouse and human autophagy proteins in IFN-γ-induced cell-autonomous responses against Toxoplasma gondii. (2014)
  • Author(s): Ohshima J, Lee Y, Sasai M, Saitoh T, Ma JS, Kamiyama N, Matsuura Y, Pann-Ghill S, Hayashi M, Ebisu S, Takeda K, Akira S, Yamamoto M
  • Journal Title: J Immunol. Volume: 192 Pages: 3328-3335
  • Peer Reviewed
• [Journal Article] The E2-Like Conjugation Enzyme Atg3 Promotes Binding of IRG and Gbp Proteins to Chlamydia- and Toxoplasma-Containing Vacuoles and Host Resistance. (2014)
  • Author(s): Haldar AK, Piro AS, Pilla DM, Yamamoto M, Coers J.
  • Journal Title: PLoS One Volume: 9
  • Peer Reviewed
• [Journal Article] Innate immune response induced by baculovirus attenuates transgene expression in mammalian cells. (2014)
  • Author(s): Ono C, Ninomiya A, Yamamoto S, Abe T, Wen X, Fukuhara T, Sasai M, Yamamoto M, Saitoh T, Satoh T, Kawai T, Ishii KJ, Akira S, Okamoto T, Matsuura Y.
  • Journal Title: J Virol. Volume: 88 Pages: 2157-67
  • Peer Reviewed
• [Journal Article] Pathogen Recognition Receptors: Ligands and Signaling Pathways by Toll-like Receptors. (2013)
  • Author(s): Sasai M, Yamamoto M
  • Journal Title: Int Rev Immunol. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] A cluster of interferon-γ-inducible p65 GTPases plays a critical role in host defense against Toxoplasma gondii (2012)
  • Author(s): Yamamoto M, Okuyama M, Ma JS, Kimura T, Kamiyama N, Saiga H, Ohshima J, Sasai M, Kayama H, Okamoto T, Huang DS, Soldati-Favre D, Horie K, Takeda J, Takeda K
  • Journal Title: Immunity Volume: 37 Pages: 302-313
  • Peer Reviewed
• [Journal Article] A cluster of interferon-γ-inducible p65 GTPases plays a critical role in host defense against Toxoplasma gondii. (2012)
  • Author(s): Yamamoto M, Okuyama M, Ma JS, Kimura T, Kamiyama N, Saiga H, Ohshima J, Sasai M, Kayama H, Okamoto T, Huang DS, Soldati-Favre D, Horie K, Takeda J, Takeda K.
  • Journal Title: Immunity Volume: 37 Pages: 302-313
  • Peer Reviewed
• [Journal Article] Inhibition of ATF6β-dependent host adaptive immune response by a Toxoplasma virulence factor ROP18 (2012)
  • Author(s): Yamamoto M, et al
  • Journal Title: Virulence Volume: 3 Pages: 1-1
  • Peer Reviewed
• [Journal Article] ATF6βis a host cellular target of the Toxoplasma gondii virulence factor ROP18 (2011)
  • Author(s): Yamamoto M, Ma JS, Mueller C, Kamiyama N, Saiga H, Kubo E, Kimura T, Okamoto T, Okuyama M, Kayama H, Nagamune K, Takashima S, Matsuura Y, Soldati-Favre D, Takeda K
  • Journal Title: J Exp Med Volume: 208 Issue: 1 Pages: 1533-1546
  • DOI: 10.4161/viru.3.1.18340
  • Peer Reviewed
• [Journal Article] ATF6β is a host cellular target of the Toxoplasma gondii virulence factor ROP18 (2011)
  • Author(s): Yamamoto M, et al
  • Journal Title: J Exp Med Volume: 208 Pages: 1533-1546
  • Peer Reviewed
• [Presentation] IFN-γ依存的抗トキソプラズマ応答におけるオートファジー蛋白質の役割 (2014)
  • Author(s): 山本雅裕、大嶋淳、馬知秀、笹井美和、李英愛
  • Organizer: 第82回日本寄生虫学会大会
  • Place of Presentation: 愛媛大学城北キャンパス、愛媛
• [Presentation] Role of the mouse and human autophagy proteins in IFN-γ-induced cell-autonomous responses against Toxoplasma gondii (2014)
  • Author(s): Ohshima J, Lee Y, Ma JS, Sasai M, Yamamoto M
  • Organizer: 第7回寄生虫感染免疫研究会
  • Place of Presentation: ベストウエスタンホテル高山、岐阜
• [Presentation] Immunological interface between host and a protozoan parasite Toxoplasma gondii (2013)
  • Author(s): Yamamoto M
  • Organizer: FORUM GRADUATE SCHOOLS INFECTION & IMMUNITY BIOLOGIE-MEDECINE
  • Place of Presentation: Geneva, Switzerland
  • Year and Date: 2013-06-28
• [Presentation] Selective and Strain-specific NFAT4 activation by a Toxoplasma gondii polymorphic Dense Granule Protein GRA6 (2013)
  • Author(s): Yamamoto M
  • Organizer: International Symposium TCUID2013 Toward Comprehensive Understanding of Immune Dynamism
  • Place of Presentation: Suita, Osaka, Japan
• [Presentation] A protozoan parasite Toxoplasma gondii manipulates host cell functions by effector molecules (2013)
  • Author(s): Yamamoto M
  • Organizer: The XIVth International Congress of Protistology, Symposium 7
  • Place of Presentation: Vancouver, Canada
• [Presentation] インターフェロン誘導性遺伝子群GBPの抗トキソプラズマ自然免疫における役割の解明 (2013)
  • Author(s): 山本雅裕、大嶋淳、馬知秀、神山長慶、竹田潔
  • Organizer: 第82回日本寄生虫学会大会
  • Place of Presentation: 東京医科歯科大学湯島キャンパス、東京
• [Presentation] A Cluster of IFN-g-inducible p65 GTPases Plays a Critical role in the Host Defense against Toxoplasma gondii (2013)
  • Author(s): 山本雅裕、馬知秀、大嶋淳、笹井美和
  • Organizer: 第6回寄生虫感染免疫研究会
  • Place of Presentation: 大分大学・医学部、大分
• [Presentation] Selective and Strain-specific NFAT4 activation by a Toxoplasma gondii polymorphic Dense Granule Protein GRA6 (2013)
  • Author(s): Yamamoto M
  • Organizer: International Symposium TCUID2013 Toward Comprehensive Understanding of Immune Dynamism
  • Place of Presentation: 吹田、大阪、日本
  • Invited
• [Presentation] インターフェロン誘導性遺伝子群GBPの抗トキソプラズマ自然免疫における役割の解明 (2013)
  • Author(s): 山本雅裕、大嶋淳、馬知秀、神山長慶、竹田潔
  • Organizer: 第82回日本寄生虫学会大会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Role of GBPs in innate host defense against an intracellular pathogen Toxoplasma gondii (2012)
  • Author(s): Yamamoto M
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 神戸国際会議場,神戸、兵庫
• [Presentation] Essential role of interferon-γ-inducible p65 GTPases in host cellular innate immunity against Toxoplasma gondii (2012)
  • Author(s): Yamamoto M
  • Organizer: The 11^<th> Awaji International Forum on Infection and Immunity
  • Place of Presentation: Awaji Yumebutai International Conference Center on Awaji Island, Hyogo, Japan
• [Presentation] Critical function of a Cluster of IFN-γ-indudible p65 GTPases in Host Defense Against Toxoplasma gondii (2012)
  • Author(s): Yamamoto M, Okuyama M, Ma JS, Kamiyama N, Ohshima J, Soldati-Favre D, Takeda J, Takeda K
  • Organizer: WHIP 2012 16^<th> Annual Woods Hole ImmunoParasitology Conference
  • Place of Presentation: Marine Biological Laboratory, Woods Hole, MA, USA
• [Presentation] Role of GBPs in innate host defense against an intracellular pathogen Toxoplasma gondii (2012)
  • Author(s): Yamamoto M
  • Organizer: 第41回日本免疫学会総会・学術集会
  • Place of Presentation: 兵庫
  • Invited
• [Presentation] A Toxoplasma virulence factor ROP18 disrupts a host innate and adaptive immune linkage (2011)
  • Author(s): 山本雅裕
  • Organizer: The Second CSI/JSI/KAI Joint Symposium on Immunology "Regulation of Immune Responses in Health and Diseases
  • Place of Presentation: Osaka University, Osaka, Japan(招待講演)
  • Year and Date: 2011-12-05
• [Presentation] A mechanism of innate immune evasion by a protozoan parasite (2011)
  • Author(s): Masahir o Yamamoto
  • Organizer: SRC Mini Symposium II"Immune Regulation & Immune Evasion"
  • Place of Presentation: UNIST, Ulsan, Koera
  • Year and Date: 2011-10-18
• [Presentation] A mechanism of innate immune evasion by a protozoan parasite (2011)
  • Author(s): 山本雅裕
  • Organizer: SRC Mini Synposium II "Immune Regulation & Immune Evasion"
  • Place of Presentation: UNIST, Ulsan, Koera(招待講演)
  • Year and Date: 2011-10-18
• [Presentation] Targeted disruption of an ATF6β-dependent host type I immunity by a Toxoplasma virulence factor ROP18 (2011)
  • Author(s): 山本雅裕
  • Organizer: IUMS2011 XIII International Congerss of Bacteriology and Applied Microbiology
  • Place of Presentation: Sapporo Convention Center, Sapporo, Japan(招待講演)
  • Year and Date: 2011-09-08
• [Presentation] ATF6b is a Host Cellular Target of the Toxoplasma Virulence factor ROP18 (2011)
  • Author(s): 山本雅裕
  • Organizer: WHIP 2011 15th Annual Woods Hole ImmunoParasitology Conference
  • Place of Presentation: Marine Biological Laboratory, Woods Hole, MA, USA
  • Year and Date: 2011-04-18
• [Presentation] A Toxoplasma virulence factor ROP18 disrupts a host innate and adaptive immune linkage (2011)
  • Author(s): Masahir o Yamamoto
  • Organizer: The Second CSI/JSI/KAI Joint Symposium on Immunology"Regulation of Immune Responses in Health and Diseases
  • Place of Presentation: Osaka University, Osaka, Japan
• [Presentation] Targeted disruption of an ATF6β-dependent host type I immunity by a Toxoplasma virulence factor ROP18 (2011)
  • Author(s): Masahir o Yamamoto, Naganori Kamiyama, Ji Su Ma, Christina Mueller, Dominique Soldati-Favre, Kiyoshi Takeda
  • Organizer: IUMS2011 XIII International Congerss of Bacteriology and Applied Microbiology
  • Place of Presentation: Sapporo Convention Center, Sapporo, Japan
• [Presentation] ATF6βis a Host Cellular Target of the Toxoplasma Virulence factor ROP18 (2011)
  • Author(s): Yamamoto M, Ma JS, Mulleler C, Kamiyama N, Soldati-Favre D, Takeda K
  • Organizer: WHIP 2011 15^<th> Annual Woods Hole ImmunoParasitology Conference
  • Place of Presentation: Marine Biological Laboratory, Woods Hole, MA, USA