The protective role of a novel population of interferon-gamma-producing cells in severe invasive group A streptococcal infections

• Project/Area Number: 22790959
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Infectious disease medicine
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: MATSUMURA Takayuki 国立感染症研究所, 免疫部, 研究員 (50434379)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 感染症防御学 / 劇症型溶血性レンサ球菌感染症 / IFN-γ / 感染症 / 細菌 / 免疫学 / 未成熟骨髄系細胞

Research Abstract

Cytokine-activated neutrophils are known to be essential for protection against group A Streptococcus (GAS) infections. However, during severe invasive GAS infections that accompanied with neutropenia, it remains unclear which factors are protective against such infections, and which cell population is the source of them. Here we show that mice infected with severe invasive GAS isolates, but not with non-invasive GAS isolates, exhibit high concentrations of plasma IFN-g during the early stage of infection. IFN-g is necessary to protect mice, and is produced by a novel population of GM-CSF-dependent immature myeloid cells with ring-shaped nuclei (IFN-g-producing immature myeloid cells; gIMCs). These gIMCs express monocyte and granulocyte markers, and also produce nitric oxide. The adoptive transfer of gIMCs ameliorates infection in wild-type and IFN-g-deficient mice. Our results indicate that gIMCs have a protective role during the early stage of severe invasive GAS infections.

Research Products

• [Journal Article] Critical roles for lipomannan and lipoarabinomannan in cell wall integrity of mycobacteria and pathogenesis of tuberculosis. (2013)
  • Author(s): Fukuda T, Matsumura T, Ato M, Hamasaki M, Nishiuchi Y, Murakami Y, Maeda Y, Yoshimori T, Matsumoto S, Kobayashi K, Kinoshita T, Morita Y.
  • Journal Title: MBio Volume: 4 Issue: 1
  • DOI: 10.1128/mbio.00472-12
  • Peer Reviewed
• [Journal Article] Interferon-γ-producing immature myeloid cells confer protection against severe invasive group A Streptococcus infections (2012)
  • Author(s): Matsumura T, Ato M, Ikebe T, Ohnishi M, Watanabe H, Kazuo Kobayashi
  • Journal Title: Nat Commun Volume: 3 Issue: 1 Pages: 678-678
  • DOI: 10.1038/ncomms1677
  • Peer Reviewed
• [Journal Article] Highly frequent mutations in negative regulators of multiple virulence genes in group A streptococcal toxic shock syndrome isolates (2010)
  • Author(s): Ikebe T, Ato M, Matsumura T, Hasegawa H, Sata T, Kobayashi K, Watanabe H
  • Journal Title: PLoS Pathog Volume: 6 Issue: 4 Pages: e1000832-e1000832
  • DOI: 10.1371/journal.ppat.1000832
  • Peer Reviewed
• [Journal Article] Identification of BCAP-(L) as a negative regulator of the TLR signaling-induced production of IL-6 and IL-10 in macrophages by tyrosine phosphoproteomics (2010)
  • Author(s): Matsumura T, Oyama M, Kozuka-Hata H, Ishikawa K, Inoue T, Muta T, Semba K, Inoue J
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 400 Pages: 265-270
  • Peer Reviewed
• [Journal Article] Highly frequent mutations in negative regulators of multiple virulence genes in group A streptococcal toxic shock syndrome isolates (2010)
  • Author(s): Tadayoshi Ikebe, Manabu Ato, Takayuki Matsumura, Hideki Hasegawa, Tetsutaro Sata, Kazuo Kobayashi, Haruo Watanabe
  • Journal Title: PLoS Pathogens Volume: 6
  • Peer Reviewed
• [Presentation] The defensive role of interferon- ・ -producing immature myeloid cells in severe invasive group A Streptococcus infections, IMMUNOLOGY 2012 (2012)
  • Author(s): Matsumura T, Ikebe T, Ohnishi M, Watanabe H, Kobayashi K, Ato M
  • Organizer: 99th Annual Meeting The American Association of Immunologists
  • Place of Presentation: Boston, MA, USA
• [Presentation] 劇症型A群レンサ球菌感染症におけるIFN-γ産生未成熟骨髄系細胞の役割 (2012)
  • Author(s): 松村隆之 , 池辺忠義 , 大西真 , 渡邉治雄 ,小林和夫 , 阿戸学
  • Organizer: 第6回細菌学若手コロッセウム
  • Place of Presentation: 東京
• [Presentation] The defensive role of interferon-γ-producing immature myeloid cells in severe invasive group A Streptococcus infections (2012)
  • Author(s): Matsumura T, Ikebe T, Ohnishi M, Watanabe H, Kobayashi K, Ato M
  • Organizer: IMMUNOLOGY 2012, 99th Annual Meeting The American Association of Immunologists
  • Place of Presentation: Boston, MA, USA
• [Presentation] 劇症型A 群レンサ球菌感染症におけるIFN-γ産生未成熟骨髄系細胞の役割 (2012)
  • Author(s): 松村 隆之, 池辺忠義, 大西真, 渡邉治雄, 小林和夫, 阿戸学
  • Organizer: 第6回細菌学若手コロッセウム
  • Place of Presentation: 東京
• [Presentation] IFN-γ-producing immature myeloid cells confer protection against severe invasive group A streptococcal infections in mice (2011)
  • Author(s): Matsumura T, Ikebe T, Ohnishi M, Watanabe H, Kobayashi K, Ato M
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-29
• [Presentation] IFN-γ-producing immature myeloid cells confer protection against severe invasive group A streptococcal infections in mice (2011)
  • Author(s): Takayuki Matsumura, Tadayoshi Ikebe, Mokoto Ohnishi, Haruo Watanabe, Kazuo Kobayashi, Manabu Ato
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2011-11-29
• [Presentation] The protective role of a novel population of interferon-γ-producing cells in severe invasive group A streptococcal infections (2011)
  • Author(s): Matsumura T, Ikebe T, Ohnishi M, Watanabe H, Kobayashi K, Ato M
  • Organizer: XVIII Lancefield International Symposium
  • Place of Presentation: Palermo, Italy
  • Year and Date: 2011-09-08
• [Presentation] The protective role of a novel population of interferon-γ-producing cells in severe invasive group A streptococcal infections (2011)
  • Author(s): Takayuki Matsumura, Tadayoshi Ikebe, Mokoto Ohnishi, Haruo Watanabe, Kazuo Kobayashi, Manabu Ato
  • Organizer: XVIII Lancefield International Symposium
  • Place of Presentation: Hilton Villa Igiea Palermo (Palermo, Italy)
  • Year and Date: 2011-09-08
• [Presentation] A novel interferon-γ-producing subpopulation of immature myeloid cells confers protection from severe invasive group A Streptococcus infections (2011)
  • Author(s): Matsumura T, Ikebe T, Ohnishi M, Watanabe H, Kobayashi K, Ato M
  • Organizer: Joint International Meeting of The 76th Annual Meeting of the Japanese Society for Interferon and Cytokine Research and The 19th International Symposium of Macrophage Molecular and Cell Biology 2011 (JSICR-MMCB 2011)
  • Place of Presentation: 大阪
  • Year and Date: 2011-05-25
• [Presentation] A novel interferon-γ-producing subpopulation of immature myeloid cells confers protection from severe invasive group A Streptococcus infections (2011)
  • Author(s): Takayuki Matsumura, Tadayoshi Ikebe, Mokoto Ohnishi, Haruo Watanabe, Kazuo Kobayashi, Manabu Ato
  • Organizer: Joint International Meeting of The 76th Annual Meeting of the Japanese Society for Interferon and Cytokine Research and The 19th International Symposium of Macrophage Molecular and Cell Biology 2011 (JSICR-MMCB 2011)
  • Place of Presentation: 全日空ゲートタワーホテル大阪(大阪)
  • Year and Date: 2011-05-25
• [Presentation] 劇症型溶血性レンサ球菌感染症における環状核骨髄系細胞の保護的役割 (2011)
  • Author(s): 松村隆之, 池辺忠義, 大西真, 渡邉治雄, 小林和夫, 阿戸学
  • Organizer: 第9回感染症沖縄フォーラム
  • Place of Presentation: 沖縄
  • Year and Date: 2011-02-10
• [Presentation] 劇症型溶血性レンサ球菌感染症における環状核骨髄系細胞の保護的役割 (2011)
  • Author(s): 松村隆之、池辺忠義、大西真、渡邉治雄、小林和夫、阿戸学
  • Organizer: 第9回感染症沖縄フォーラム
  • Place of Presentation: 沖縄国民年金健康センター(沖縄県)
  • Year and Date: 2011-02-10
• [Presentation] Identification of IFN-γ producing cells in severe invasive group A streptococcal infection (2010)
  • Author(s): Matsumura T, Ikebe T, Watanabe H, Kobayashi K, Ato M
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-25
• [Presentation] Identification of IFN-γ producing cells in severe invasive group A streptococcal infection (2010)
  • Author(s): Takayuki Matsumura, Tadayoshi Ikebe, Haruo Watanabe, Kazuo Kobayashi, Manabu Ato
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸ポートピアホテル(兵庫県)
  • Year and Date: 2010-08-25
• [Presentation] The defensive role of interferon-γ produced by myeloid cells in invasive group A Streptococcus infection (2010)
  • Author(s): Matsumura T, Ikebe T, Watanabe H, Kobayashi K, Ato M
  • Organizer: 18th International Symposium on Molecular Cell Biology of Macrophages 2010
  • Place of Presentation: 熊本
  • Year and Date: 2010-05-20
• [Presentation] The defensive role of interferon-γ produced by myeloid cells in invasive group A Streptococcus infection (2010)
  • Author(s): Takayuki Matsumura, Tadayoshi Ikebe, Haruo Watanabe, Kazuo Kobayashi, Manabu Ato
  • Organizer: 18^<th> International Symposium on Molecular cell biology of Macrophages 2010
  • Place of Presentation: くまもと県民交流館(熊本県)
  • Year and Date: 2010-05-20
• [Book] Myeloid-derived suppressor cells and their related cell subpopulations (The Research and Biology of Cancer I) (2013)
  • Author(s): Matsumura T, Kobayashi K, Ato M
  • Total Pages: 18
  • Publisher: iConcept Press Ltd
• [Remarks] インターフェロンγを産生する未熟骨髄系細胞は劇症型A群レンサ球菌感染に対して防御的に働く
  • URL: http://www.nih.go.jp/niid/ja/basic-science/iummunology/1717-imm-2012-001.html
• [Remarks] インターフェロンγを産生する未熟骨髄系細胞は劇症型A群レンサ球菌感染に対して防御的に働く
  • URL: http://www.nih.go.jp/niid/ja/basic-science/iummunology/1717-imm-2012-001.html
• [Remarks]
  • URL: http://www.nih.go.jp/niid/ja/basic-science/iummunology/1717-imm-2012-001.html