Role of structural alteration of bacterial lipopolysaccharide on bacterial evasion of host innate immune responses

• Project/Area Number: 24590523
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Kyoto University
• Principal Investigator: MATSUURA Motohiro 京都大学, 医学(系)研究科(研究院), 非常勤講師 (20150089)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 細菌リポ多糖LPS / 自然免疫 / 細菌感染 / 免疫回避 / TLR4

Outline of Final Research Achievements

Salmonella Typhimurium was used as representative Gram-negative bacteria and generated mutant strains having reduced number of acyl groups in its lipopolysaccharide (LPS). Culture cells of mouse and human origins were infected by the wild and mutant strains and revealed the effect of structural alterations of LPS to less-acylated types on evasion of host innate immune responses that lead to enhancement of bacterial pathogenicity. Among the markers of innate immune responses, cytokine inducing activity was down-regulated by the less-acylated mutants in human cells largely caused by evasion of TLR4 stimulation. While phagocytic activity was weakened by the mutants even in mouse cells without TLR4 dependency and this evasion was suggested to occur generally in wide variety of host origins.

Research Products

• [Journal Article] Structural modification of bacterial lipopolysaccharide that facilitate Gram-negative bacteria evasion of host innate immunity (2013)
  • Author(s): Motohiro Matsuura
  • Journal Title: Frontiers in Immunology Volume: 4 Pages: 1-9
  • DOI: 10.3389/fimmu.2013.00109
  • NAID: 120005333787
  • Peer Reviewed
• [Journal Article] Evasion of human innate immunity without antagonizing TLR4 by mutant Salmonella enterica serovar Typhimurium having penta-acylated lipid A (2012)
  • Author(s): M. Matsuura, K. Kawasaki, K. Kawahara and M. Mitsuyama
  • Journal Title: Innate Immunity Volume: 18 Issue: 5 Pages: 764-773
  • DOI: 10.1177/1753425912440599
  • NAID: 120005398390
  • Peer Reviewed
• [Journal Article] Listeria monocytogenes strain-specific impairment of the TetR regulator underlies the drastic increase in cyclic di-AMP secretion and beta interferon-inducing ability (2012)
  • Author(s): Yamamoto T, Hara H, Tsuchiya K, Sakai S, Fang R, Matsuura M, Nomura T, Sato F, Mitsuyama M, Kawamura I
  • Journal Title: Infect Immun Volume: 80 Issue: 7 Pages: 2323-2332
  • DOI: 10.1128/iai.06162-11
  • Peer Reviewed
• [Presentation] リピドＡアシル基数減少がグラム陰性菌の病原性増強に果たす役割 (2014)
  • Author(s): 松浦基博
  • Organizer: 第２０回日本エンドトキシン・自然免疫研究会
  • Place of Presentation: 順天堂大学本郷キャンパス
  • Year and Date: 2014-12-05 – 2014-12-06
• [Presentation] Modification of lipid A structure in lipopolysaccharide of Yersinia pestis that fasilitate bacterial evasion of human innate immunity (2013)
  • Author(s): Motohiro Matsuura
  • Organizer: Cold Spring Harbor Asia Conferences, Yersinia 11 - the 11th international symposium on Yersinia
  • Place of Presentation: 中国、蘇州市
  • Invited
• [Presentation] Evasion of human innate immunity without antagonizing TLR4 by mutant Salmonella enterica serovar Typhimurium having penta-acylated lipid A (2012)
  • Author(s): M. Matsuura, K. Kawasaki, K. Kawahara and M. Mitsuyama
  • Organizer: European Congress of Immunology
  • Place of Presentation: Scottish Exhibition & Conference Centre (Glasgow, England)
• [Book] エンドトキシン・自然免疫研究 (2016)
  • Author(s): 松浦基博（編集：長岡功 他）
  • Publisher: 医学図書出版株式会社