Development of novel therapies using neutrophil functions mediated by the autophagy machinery against multi-drug resistant bacterial infections

• Project/Area Number: 26670484
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Infectious disease medicine
• Research Institution: Kyoto University
• Principal Investigator: ITOH Hiroshi 京都大学, 医学(系)研究科(研究院), 助教 (20362387)
• Co-Investigator(Renkei-kenkyūsha): ADACHI Souichi 京都大学, 大学院医学研究科, 教授 (10273450)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 好中球 / オートファジー / 自然免疫 / 殺菌能 / 多剤耐性菌 / 易感染宿主 / 貪食 / 免疫グロブリン / 易感染性宿主

Outline of Final Research Achievements

We revealed the enhancing effects on phagocytic function, bactericidal activity, and autophagy of human neutrophils by an intravenous immunoglobulin preparation in the experimental system using clinical isolate multidrug-resistant bacteria. We also observed that the number of bacteria-containing autophagosomes have increased in the experimental system. In addition, we revealed that the autophagy contributes the bactericidal activity of neutrophils by the autophagy suppression experiments. The similar effects were also observed in neutrophils isolated from the patients being administered immunosuppressive agents after hematopoietic stem cell transplantation. It is expected that the therapy with neutrophil functions mediated by the autophagy machinery will be established effectively against multi-drug resistant bacterial infections in compromised hosts.

Research Products

• [Journal Article] Intravenous immunoglobulin enhances the killing activity and autophagy of neutrophils isolated from immunocompromised patients against multidrug-resistant bacteria. (2015)
  • Author(s): Matsuo H, Itoh H, Kitamura N, Kamikubo Y, Higuchi T, Shiga S, Ichiyama S, Kondo T, Takaori-Kondo A, Adachi S.
  • Journal Title: Biochem Biophys Res Commun. Volume: 464 Issue: 1 Pages: 94-9
  • DOI: 10.1016/j.bbrc.2015.06.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Adverse prognostic impact of KIT mutations in childhood CBF-AML: the results of the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 trial. (2015)
  • Author(s): Tokumasu M, Murata C, Shimada A, Ohki K, Hayashi Y, Saito AM, Fujimoto J, Horibe K, Nagao M, Itoh H, Kamikubo Y, Nakayama H, Kinoshita A, Tomizawa D, Taga T, Tawa A, Tanaka S, Heike T, Adachi S
  • Journal Title: Leukemia Volume: 29 Issue: 12 Pages: 2438-2441
  • DOI: 10.1038/leu.2015.121
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Enhancement of neutrophil autophagy by an IVIG preparation against multi-drug-resistant bacteria as well as drug sensitive strains. (2015)
  • Author(s): Itoh H, Matsuo H, Kitamura N, Yamamoto S, Higuchi T, Takematsu H, Kamikubo Y, Kondo T, Yamashita K, Sasada M, Takaori-Kondo A, Adachi S.
  • Journal Title: Journal of Leukocyte Biology Volume: 98 Issue: 1 Pages: 107-117
  • DOI: 10.1189/jlb.4a0813-422rrr
  • Peer Reviewed / Open Access
• [Journal Article] Autocrine pathways involving S100A8 and/or S100A9 that are postulated to regulate the immunological functions of macrophages in rats. (2015)
  • Author(s): Okada K, Arai S, Nakase H, Kohno H, Nakamura F, Takeda M, Toda Y, Itoh H, Adachi S, Ikemoto M
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 456 Issue: 1 Pages: 415-420
  • DOI: 10.1016/j.bbrc.2014.11.099
  • Peer Reviewed
• [Journal Article] EVI1 overexpression is a poor prognostic factor in pediatric patients with mixed lineage leukemia-AF9 rearranged acute myeloid leukemia. (2014)
  • Author(s): Matsuo H, Kajihara M, Tomizawa D, Watanabe T, Saito AM, Fujimoto J, Horibe K, Kodama K, Tokumasu M, Itoh H, Nakayama H, Kinoshita A, Taga T, Tawa A, Taki T, Shiba N, Ohki K, Hayashi Y, Yamashita Y, Shimada A, Tanaka S, Adachi S.
  • Journal Title: Haematologica Volume: 99 Issue: 11 Pages: 225-227
  • DOI: 10.3324/haematol.2014.107128
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group. (2014)
  • Author(s): Matsuo H, Kajihara M, Tomizawa D, Watanabe T, Saito AM, Fujimoto J, Horibe K, Kodama K, Tokumasu M, Itoh H, Nakayama H, Kinoshita A, Taga T, Tawa A, Taki T, Tanaka S, Adachi S.
  • Journal Title: Blood Cancer J Volume: 4 Issue: 7 Pages: e226-e226
  • DOI: 10.1038/bcj.2014.47
  • Peer Reviewed / Open Access
• [Presentation] ヒト前骨髄球性白血病細胞株HL60を用いたオートファジー解析実験系の確立 (2015)
  • Author(s): 伊藤洋志、山本翔、谷村志桜里、上久保靖彦、足立壯一
  • Organizer: 第26回日本生体防御学会学術総会
  • Place of Presentation: 台東区生涯学習センター ミレニアムホール
  • Year and Date: 2015-07-10
• [Presentation] 真菌感染症の治療における好中球の殺菌能の意義 (2014)
  • Author(s): 北村奈緒子、山本翔、伊藤洋志、足立壯一
  • Organizer: 日本Cell Death学会
  • Place of Presentation: 東京医科歯科大学 鈴木章夫記念講堂 （東京都文京区）
  • Year and Date: 2014-07-18 – 2014-07-19
• [Presentation] 好中球の殺菌能におけるオートファジー機構の役割 (2014)
  • Author(s): 伊藤洋志、北村奈緒子、山本翔、松尾英将、足立壯一
  • Organizer: 日本生体防御学会
  • Place of Presentation: 東北大学 片平さくらホール （宮城県仙台市青葉区）
  • Year and Date: 2014-07-09 – 2014-07-11
• [Remarks] 京都大学大学院医学研究科人間健康科学系専攻 血液・生体防御学研究室 研究業績(2009年度以降のみ）
  • URL: http://adachilab.web.fc2.com/paper.html#2015
• [Remarks] 長浜バイオ大学 教員の研究紹介
• [Remarks] 京都大学大学院医学研究科 人間健康科学系専攻 検査応用開発学分野 血液・生体防御学研究室ホームページ
  • URL: http://adachilab.web.fc2.com/index.html