Role of IFN-gamma in elimination of intracellularly invaded oral bacteria and disease progression.

• Project/Area Number: 15H06382
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Conservative dentistry
• Research Institution: Osaka University
• Principal Investigator: Ohshima Jun 大阪大学, 歯学研究科, 助教 (30755450)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 微生物学 / 歯学 / 微生物 / 細菌 / 感染症 / 免疫学

Outline of Final Research Achievements

The purpose of this study was to investigate the binding molecule of Gbp, a kind of IFN-gamma-inducible GTPase, and to try to elucidate the regulatory mechanism of IFN-gamma-induced GTPases' function.　In addition, we aimed to clarify the mechanism of progression and prolongation of periodontal disease by examining the relationship between host defense through IFN-gamma and oral bacteria invading into the host cells. As a result, we were able to identify RabGDI-alpha as a novel molecule that binds to Gbp2 and negatively regulates its function. Also, it was suggested that IFN-gamma is involved in elimination of intracellularly invaded oral bacteria and subsequent production of inflammatory cytokines and that P. gingivalis has an unknown mechanism to negatively control IFN-signaling.

Research Products

• [Journal Article] RabGDIα is a negative regulator of interferon-γ-inducible GTPase-dependent cell-autonomous immunity to Toxoplasma gondii. (2015)
  • Author(s): Ohshima J, Sasai M, Liu J, Yamashita K, Ma JS, Lee Y, Bando H, Howard JC, Ebisu S, Hayashi M, Takeda K, Standley DM, Frickel EM, Yamamoto M.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. Volume: 112
  • DOI: 10.1073/pnas.1510031112
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] mTOR Complex Signaling through the SEMA4A-Plexin B2 Axis Is Required for Optimal Activation and Differentiation of CD8+ T Cells. (2015)
  • Author(s): Ito D, Nojima S*, Nishide M, Okuno T, Takamatsu H, Kang S, Kimura T, Yoshida Y, Morimoto K, Maeda Y, Hosokawa T, Toyofuku T, Ohshima J, Kamimura D, Yamamoto M, Murakami M, Morii E, Rakugi H, Isaka Y, Kumanogoh A*. (* correspondence)
  • Journal Title: J Immunol Volume: 195 Pages: 934-43
  • DOI: 10.4049/jimmunol.1403038
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] p62 Plays a Specific Role in Interferon-γ-Induced Presentation of a Toxoplasma Vacuolar Antigen. (2015)
  • Author(s): Lee Y, Sasai M, Ma JS, Sakaguchi N, Ohshima J, Bando H, Saitoh T, Akira S, Yamamoto M
  • Journal Title: Cell Rep. Volume: 13 Pages: 223233-223233
  • DOI: 10.1016/j.celrep.2015.09.005
  • NAID: 120007001422
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] RabGDIα is a negative regulator of interferon-γ-inducible GTPase-dependent cell-autonomous immunity to Toxoplasma gondii. (2015)
  • Author(s): Sasai M, Ohshima J, Ma JS, Lee Y, Takeda K, Yamamoto M.
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2015-11-19
• [Presentation] p62 plays a specific role in IFN-g-induced presentation of a Toxoplasma vacuolar antigen. (2015)
  • Author(s): Lee Y, Sasai M, Ma JS, Sakaguchi N, Ohshima J, Bando H, Saitoh T, Akira S, and Yamamoto M.
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道札幌市）
  • Year and Date: 2015-11-19
• [Presentation] Selective and strain-specific NFAT4 activation by the Toxoplasma gondii polymorphic dense granule protein GRA6. (2015)
  • Author(s): Ma JS, Sasai M, Ohshima J, Lee Y, Bando H, Takeda K, and Yamamoto M.
  • Organizer: Forum Cheju17
  • Place of Presentation: Taniguchi Memorial Hall, Research Institute for Microbial Diseases, Osaka University（大阪府吹田市）
  • Year and Date: 2015-11-13
  • Int'l Joint Research
• [Presentation] p62 plays a specific role in IFN-g-induced presentation of a Toxoplasma vacuolar antigen. (2015)
  • Author(s): Lee Y, Sasai M, Ma JS, Sakaguchi N, Ohshima J, Bando H, Saitoh T, Akira S, and Yamamoto M.
  • Organizer: Forum Cheju17
  • Place of Presentation: Taniguchi Memorial Hall, Research Institute for Microbial Diseases, Osaka University（大阪府吹田市）
  • Year and Date: 2015-11-13
  • Int'l Joint Research