Molecular mechanisms of intracellular survival of M. tuberculosis inside host macrophages via regulation of caspases activation.

• Project/Area Number: 20790334
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Bacteriology (including Mycology)
• Research Institution: Hyogo College of Medicine
• Principal Investigator: UCHIYAMA Ryosuke Hyogo College of Medicine, 医学部, 助教 (20456891)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 結核菌 / マクロファージ / カスパーゼ / IL-18 / FasL / Fasシグナル / 細胞内寄生菌 / 炎症性サイトカイン

Research Abstract

On the basis of regulation of caspase(s) in host macrophages infected with M. tuberculosis (MTB) and the typical intracellular bacteria L. monocytogenes (LM), we have shown that caspase-1 activation was induced in macrophages infected with MTB, which leads to the production of functional inflammatory cytokines IL-1β and IL-18. We also found that the virulence factor RD1 of MTB involved in the activation of caspase-1 in macrophages. FasL/Fas signaling pathway is an important systems for caspase(s) activation. We have unveiled the involvement of Fas signaling pathway for IL-18 production in mice infected with BCG or LM.

Research Products

• [Journal Article] IFN-γ is a master regulator of endotoxin shock syndrome in mice primed with heat-killed Propionibacterium acnes (2010)
  • Author(s): Kawa K, Tsutsui H, Uchiyama R, Kato J, Matsui K, Iwakura Y, Matsumoto T, Nakanishi K.
  • Journal Title: International Immunology 22 Pages: 157-166
  • NAID: 10027391627
  • Peer Reviewed
• [Journal Article] The RD1 locus in the Mycobacterium tuberculosis genome contributes to activation of caspase-1 via induction of potassium ion efflux in infected macrophages. (2009)
  • Author(s): Kurenuma T, Kawamura I, Hara H, Uchiyama R, Daim S, Dewamitta SR, Sakai S, Tsuchiya K, Nomura T, Mitsuyama M.
  • Journal Title: Infect. Immun. 77(9) Pages: 3992-4001
  • Peer Reviewed
• [Journal Article] Phosphocholine-containing glycosyl inositol-phosphoceramides from Trichoderma viride induce defense responses in cultured rice cells (2009)
  • Author(s): Uchiyama R., Aoki K, Sugimoto H., Taka N., Katayama T., Itonori S., Sugita M., Che FS., Kumagai H., Yamamoto K
  • Journal Title: Biosci. Biotechnol. Biochem 73(1) Pages: 74-78
  • NAID: 10027535958
  • Peer Reviewed
• [Journal Article] Contribution of TIR domain-containing adapter inducing IFN-β-mediated IL-18 release to LPS-induced liver injury in mice (2009)
  • Author(s): Imamura M., Tsutsui H., Yasuda K., Uchiyama R., Yumikura-Futatsugi S, Mitani K., Hayashi S., Akira S., Taniguchi S., Van Rooijen N., Tschopp J., Yamamoto T., Fujimoto J., Nakanishi K.
  • Journal Title: J. Hepatol (In press)
  • Peer Reviewed
• [Presentation] 細菌感染におけるFasシグナル系を介したIL-18産生機構 (2010)
  • Author(s): 内山良介
  • Organizer: 第83回日本細菌学会総会
  • Place of Presentation: 横浜(パシフィコ横浜)
  • Year and Date: 2010-03-28
• [Presentation] RD1 locus in Mycobacterium tuberculosis genome contributes to the activation of caspase-1 via induction of potassium efflux in infected macrophages. (2009)
  • Author(s): Dewamitta SR., Kawamura I., Hara H., Uchiyama R., Daim S., Sakai S., Tsuchiya K., Nomura T, Mitsuyama M.
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪(国際会議場)
  • Year and Date: 2009-12-03
• [Presentation] 細菌感染におけるFas/FasLシグナルを介したIL-18産生機序の解析 (2009)
  • Author(s): 内山良介
  • Organizer: 第82日本細菌学総会
  • Place of Presentation: 名古屋(名古屋国際会議場)
  • Year and Date: 2009-03-13
• [Remarks]
  • URL: http://www.hyo-med.ac.jp/department/micro/index.htm
• [Remarks]
  • URL: http://www.hyo-med.ac.jp/department/micro/index.htm