リューシュマニア感染における慢性炎症によるリンパ組織破壊と免疫不全機構の解明

• Project/Area Number: 19590506
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: 阿戸 学 National Institute of Infectious Diseases, 免疫部, 室長 (20392318)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 細胞・組織 / 免疫学 / 慢性感染 / 炎症 / ストローマ

Research Abstract

内蔵リューシュマニア症は、Leishmania donovaniによって起こる熱帯伝染病で、放置すると死に至る。有効なワクチンはなく、宿主免疫機構が感染の進行を阻止できない理由は未だ不明である。
本研究は、L. donovani感染マウスモデルを用いて、感染臓器のマクロファージとストローマ細胞をそれぞれ感染細胞と非感染細胞に分離精製し、慢性感染に伴う炎症によるリンパ組織破壊と免疫応答障害に関与する分子を同定する事を目的とした。
脾臓マクロファージに感染するが、脾臓ストローマ細胞に対する感染は認められない原虫株と、両細胞に感染する原虫を用いて、感染脾臓よりストローマ細胞を分離して遺伝子発現を比較した所、両細胞に感染能を有する原虫感染群においてのみ、ストローマ細胞のケモカインCCL19およびCCL21発現の減少が認められた。以上より、L. donovaniのストローマ細胞直接感染によりT細胞免疫応答に必要なケモカインの産生を抑制し、免疫応答を障害していることが示唆された。

Research Products

• [Journal Article] Human Polymorphonuclear Neutrophil Responses to Burkholderia pseudomallei in Healthy and Diabetic Subjects. (2009)
  • Author(s): Chanchamroen1 S, Kewcharoenwong1 C, Susaengrat W, Ato M, Lertmemongkolchai G.
  • Journal Title: Infect Immunity. 77(1) Pages: 456-63
• [Journal Article] Human Polymorphonuclear Neutrophil Responses to Burkholderia pseudomallei in Healthy and Diabetic Subjects (2009)
  • Author(s): Chanchamroenl S, Kewcharoenwongl C, Susaengrat W, Ato M, Lertmemongkolchai G.
  • Journal Title: Infection and Immunity 77 Pages: 456-463
  • Peer Reviewed
• [Journal Article] Incompetence of neutrophils to severe invasive group A streptococcus isolates is attributed to enhancing expression of plural virulence factors by null-function of a regulatory gene. (2008)
  • Author(s): Ato M, Ikebe T, Kawabata H, Takemori T, Watanabe H.
  • Journal Title: PLoS ONE. 3(10)
• [Journal Article] Allograft inflammatory factor-1 augments macrophage phagocytotic activity and accelerates the progression of atherosclerosis in ApoE-/- mice. (2008)
  • Author(s): Mishima T, Iwabuchi K, Fujii S, Tanaka SY, Ogura H, Watano-Miyata K, Ishimori N, Andoh Y, Nakai Y, Iwabuchi C, Ato M, Kitabatake A, Tsutsui H, Onoe K.
  • Journal Title: Int J Mol Med. 21(2) Pages: 181-7
• [Journal Article] Incompetence of neutrophils to severe invasive group A streptococcus isolates is attributed to enhancing expression of plural virulence factors by null-function of a regulatory gene. (2008)
  • Author(s): Ato M, Ikebe T, Kawabata H, Takemori T, Watanabe H.
  • Journal Title: PLoS ONE 3
  • Peer Reviewed
• [Journal Article] Allograft inflammatory factor-1 augments macrophage phagocytotic activity and accelerates the progression of atherosclerosis in ApoE-/-mice. (2008)
  • Author(s): (1)Tetsuya Mishima, Kazuya Iwabuchi, Satoshi Fujii, Shinya Tanaka, Hisako Ogura, Keiko Watano-Miyata, Naoki Ishimori, Yasuhiro Andoh, Yukihito Nakai, Chikako Iwabuchi, Manabu Ato, Akira Kitabatake, Hiroyuki Tsutsui, Kazunori Onoe
  • Journal Title: International Journal of Molecular Medicine 21 Pages: 181-18
  • Peer Reviewed
• [Presentation] Host immune responses to Leishmania donovani infection : change from acute phase to chronic phase (2007)
  • Author(s): Ato M
  • Organizer: 16th Internatinal Symposium on Molecular Cell Biology of Macrophage 2007
  • Place of Presentation: 静岡
  • Year and Date: 2007-06-15
• [Presentation] Host immune responses to Leishmania donovani infection:change from acute phase to chronic phase (2007)
  • Author(s): Manabu Ato
  • Organizer: 16^<th> Internatinal Symposium on Molecular Cell Biology of Macrophage 2007
  • Place of Presentation: 静岡
  • Year and Date: 2007-06-15