The analysis of the mouse model for streptococcal toxic shock-like syndrome

• Project/Area Number: 18591112
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Kyushu University
• Principal Investigator: KUSUHARA Koichi (2008) Kyushu University, 大学院・医学研究院, 准教授 (20243941); 齋藤 光正 (2006-2007) Kyushu University, 医学研究院, 助教 (00315087)
• Co-Investigator(Kenkyū-buntansha): 楠原 浩一 九州大学, 大学院・医学研究院, 准教授 (20243941)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,060,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥660,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
• Keywords: 小児感染症学 / 劇症型A群レンサ球菌感染症 / 動物モデル / 遅延死 / 莢膜 / hasA / LPS / ヒアルロン酸 / TNF-α

Research Abstract

A 群レンサ球菌をddYマウスに筋注すると、感染の急性期から回復し、外見上は一旦健康を取り戻すにもかかわらず、約3週以降に敗血症や軟部組織壊死を伴って突然死亡し始める。研究代表者らはこの死を「遅延死delayed death」と命名し、劇症型感染症の動物モデルであると考えた.
このモデルを解析した結果、遅延死の病態に最も深く関与しているのはサイトカインストームであることが示唆された。急性死の場合と異なり、炎症性サイトカインのみならずIL-10に代表される抗炎症性サイトカインも増加しているのが特徴的で、これが免疫機能低下を引き起こし、莢膜発現菌の自由な増殖を許していると考えられた。

Research Products

• [Journal Article] High mobility group box 1(HMGB1)and macrophage migration inhibitory factor(MIF)in Kawasaki disease (2008)
  • Author(s): Hoshina T, Kusuhara K, Ikeda K, Mizuno Y, Saito M, Hara T
  • Journal Title: Scand J Rheumatol 37 Pages: 445-9
• [Journal Article] Concerted action of lactate oxidase and pyruvate oxidase in aerobic growth of Streptococcus pneumoniae : role of lactate as an energy source (2008)
  • Author(s): TaniaiH, Iida K, Seki M, Saito M, Shiota S, Nakayama H, Yoshida S
  • Journal Title: J Bacteriol 190 Pages: 3572-9
• [Journal Article] An echovirus type 18 outbreak in a neonatal intensive care unit (2008)
  • Author(s): Kusuhara K, Saito M, Sasaki Y, Hikino S, Taguchi T, Suita S, Hayashi J, Wakatsuki K, Hara T
  • Journal Title: Eur J Pediatr 167 Pages: 587-9
• [Journal Article] Onset of streptococcal toxic shock syndrome is accelerated by bruising in a mouse model (2008)
  • Author(s): Seki M, Saito M, Iida K, Taniai H, Soejima T, Nakayama H, Yoshida SI
  • Journal Title: Microbial Pathogenesis 44 Pages: 339-43
• [Journal Article] High mobility group box 1 (HMGB1)and macrophage migration inhibitory factor (MIF) in Kawasaki disease. (2008)
  • Author(s): Hoshina T, Kusuhara K, et al
  • Journal Title: Scand J Rheumatol 37 Pages: 445-449
  • Peer Reviewed
• [Journal Article] Concerted action of lactate oxidase and pyruvate oxidase in aerobic growth of Streptococcus pneumoniae : role of lactate as an energy source. (2008)
  • Author(s): Taniai H, Saito M, et al
  • Journal Title: J Bacteriol 190 Pages: 3572-3579
  • Peer Reviewed
• [Journal Article] Onset of streptococcal toxic shock syndrome is accelerated by bruising in a mouse model. (2008)
  • Author(s): Seki M, Saito M, et al
  • Journal Title: Microbial Pathogenesis 44 Pages: 339-343
  • Peer Reviewed
• [Journal Article] Onset of streptococcal toxic shock syndrome is accelerated by bruisingin a mouse model (2008)
  • Author(s): Seki M, et. al.
  • Journal Title: Microb Pathog 44 Pages: 339-343
  • Peer Reviewed
• [Journal Article] A novel agar medium to detect hydrogen peroxide-producing bacteria based on the Prussian blue-forming reaction (2007)
  • Author(s): Saito M, Seki M, Iida K, Nakayama H, Yoshida SI
  • Journal Title: Microbiol Immunol 51 Pages: 889-92
  • NAID: 10020279355
• [Journal Article] Pyogenic splenic abscess in an infant with serological evidence of cat scratch disease (2007)
  • Author(s): Kusuhara K, Nakao F, Saito M, Nakamura K, Ieiri S, Taguchi T, Hara T
  • Journal Title: Eur J Pediatr 166 Pages: 1289-91
• [Journal Article] Novel roles of osteopontin and CXC chemokine ligand 7 in the defense against mycobacterial infection (2007)
  • Author(s): Khajoee V, Saito M, Takada H, Nomura A, Kusuhara K, Yoshida S, Yoshikai Y, Hara T
  • Journal Title: Clin Exp Immunol 143 Pages: 260-8
• [Journal Article] A novuel agar mdeium to detect hydrogen peroxide-producing bacteria basde on the Prussian blue-forming reaction (2007)
  • Author(s): Saito M, et. al.
  • Journal Title: Microbiol Immunol 51 Pages: 889-892
  • Peer Reviewed
• [Journal Article] 劇症型A群レンサ球菌感染症のマウスモデルによる病態解明 (2006)
  • Author(s): 齋藤光正, 梶原英子, 吉田眞一
  • Journal Title: 福岡医学雑誌 97 Pages: 203-4
• [Journal Article] Capsule of Streptococcus pyogenes is essential for delayed death of mice in an animal model of streptococcal toxic shock syndrome (2006)
  • Author(s): Iida K, Seki M, Saito M, Kawamura Y, Kajiwara H, Nakayama H, Yoshida S
  • Journal Title: Microbiol Immunol 50 Pages: 127-30
• [Journal Article] Serum immunoglobulin levels do not affect antibody responses to influenza HA vaccine in preterm infants (2006)
  • Author(s): Sasaki Y, Kusuhara K, Saito M, Hikino S, Murayama Y, Yamashita H, Matsumoto N, Kukita J, Kinukawa N, Hara T
  • Journal Title: Vaccine 24 Pages: 2208-12
• [Journal Article] Benign convulsion with mildgastroenteritis and benign familial infantile seizure (2006)
  • Author(s): Sakai Y, Kira R, Torisu H, Yasumoto S, Saito M, Kusuhara K, Hara T
  • Journal Title: Epilepsy Res 68 Pages: 269-71
• [Journal Article] Novel roles of osteopontin and CXC chemokine ligand 7 in the defense against mycobacterial infection. (2006)
  • Author(s): Khajoee V, et al.
  • Journal Title: Clin Exp Immunol 143 Pages: 260-268
• [Journal Article] Capsule of Streptococcus pyogenes is essential for delayed death of mice in an animal model of streptococcal toxic shock syndrome. (2006)
  • Author(s): Iida K, et al.
  • Journal Title: Microbiol Immunol 50 Pages: 127-130
• [Journal Article] Serum immunoglobulin levels do not affect antibody responses to influenza HA vaccine in preterm infants. (2006)
  • Author(s): Sasaki Y, et al.
  • Journal Title: Vaccine 24 Pages: 2208-2212
• [Journal Article] Benign convulsion with mild gastroenteritis and benign familia infantile seizure. (2006)
  • Author(s): Sakai Y, et al.
  • Journal Title: Epilepsy Res 68 Pages: 269-271