Oligosaccharide administration improved clearance of infectious pathogens in acute inflammatory phase

• Project/Area Number: 25461518
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Fukushima Medical University
• Principal Investigator: Yamamoto Natsuo 福島県立医科大学, 医学部, 准教授 (50466562)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: IL-13 / TGFβ / 炎症性サイトカイン / Th1関連応答 / インフラマソーム / オリゴ多糖体 / 静脈感染 / IL-1β / 樹状細胞 / リンパ節 / ゼプシス / 初期抗体 / TNFα / バイオマーカー / 炎症蛋白 / IgM / 自然抗体 / 血流感染 / 抗炎症作用

Outline of Final Research Achievements

To clarify a role of IL-13 in early host resistance to streprococci, and C. albicans, murine airway and intravenous infection models were used. A low dose administration of these pathogens induced natural and early acquired IgM protection, while high dose administration promoted rapid local inflammatory responses to lung and kidney as infected local organs. In high dose administration, IL-13 suppressed IL-1β, CXCL２ and TNFα that may be detrimental to host for pathogen elimination. However late IL-17A was dependent on TGFβ synthesis, which is also strictly dependent on IL-13. This anti-inflammatory role of IL-13 may be promoted with a chitin-oligomer as an oligosaccharides. Oligosaccharide-IL-13-TGFβ cascades may become more critical for a recovery from sepsis as it suppresses an excessive inflammasome activation during a fatal septic condition. The in vivo finding above was supported in vitro tests of bone-marrow derived cells with additional recombinant (r)IL-13, and rTGFβ.

Research Products

• [Journal Article] Expression of activation-induced cytidine deaminase enhances the clearance of pneumococcal pneumonia: evidence of a subpopulation of protective anti-pneumococcal B1a cells (2016)
  • Author(s): Yamamoto Natsuo, Kerfoot SM, Hutchinson AT, Dela Cruz CS, Nakazawa N, Szczepanik M, Majewska-Szczepanik M, Nazimek K, Ohana N, Bryniarski K, Mori T, Muramatsu M, Kanemitsu K, Askenase PW
  • Journal Title: Immunology Volume: 147 Issue: 1 Pages: 97-113
  • DOI: 10.1111/imm.12544
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A subset of AID-dependent B-1a cells initiates hypersensitivity and pneumococcal pneumonia resistance (2016)
  • Author(s): Askenase PW, Bryniarski K, Paliwal V, Kerfoot SM, Hutchinson AT, van Loveren H, Campos R, Itakura Atsuko, Majewska-Szczepanik M, Yamamoto Natsuo, Nazimek K, Szcepanik M, Ptak W
  • Journal Title: Annals of the New York Academy of Sciences Volume: 1362 Issue: 1 Pages: 200-214
  • DOI: 10.1111/nyas.12975
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 感染症に関わる新しい炎症の概念と感染制御 (2016)
  • Author(s): 山本夏男、仲村 究、金光敬二
  • Journal Title: 臨床微生物学雑誌 Volume: 26 Pages: 1-12
  • NAID: 40020896860
• [Journal Article] Epicutaneous immunization with phosphorylcholine conjugated to bovine serum albumin (PC-BSA) and TLR9 ligand CpG alleviates pneumococcal pneumonia in mice (2014)
  • Author(s): Majewska-Szczepanik M, Yamamoto N, Askenase PW, Szczepanik M.
  • Journal Title: Pharmacological Reports Volume: 66 Issue: 4 Pages: 570-5
  • DOI: 10.1016/j.pharep.2014.02.023
  • Peer Reviewed / Open Access
• [Journal Article] Epicutaneous immunization with phosphorylcholine conjugated to bovine serum albumin (PC-BSA) and TLR9 ligand CpG alleviates pneumococcal pneumonia in mice (2014)
  • Author(s): Majewska M, Yamamoto N, Askenase PW, Szczepanik M
  • Journal Title: Pharmacological Reportｓ Volume: 66 Pages: 40-48
  • Peer Reviewed
• [Journal Article] Defect of CARD9 leads to impaired accumulation of IFN-γ -producing memory-phenotype T cells in lungs and increased susceptibility to pulmonary infection with Cryptococcus neoformans (2014)
  • Author(s): Yamamoto H, Nakamura Y, Sato K, Takahashi Y, Nomura T, Miyasaka T, Ishii K, Hara H, Yamamoto N, Kanno E, Iwakura Y, Kawakami K
  • Journal Title: Infect. Immun Volume: 82 Issue: 4 Pages: 1606-1615
  • DOI: 10.1128/iai.01089-13
  • Peer Reviewed
• [Presentation] IL-13-dependent biomarkers with liver differentiation after pneumococcal sepsis during rapid inflammatory phase (2016)
  • Author(s): Yamamoto N, Nakamura K, Arai K, Dela Cruz C, Machida T, SUzuki Y, Ogura Y, Abe Y, Sekine H, Iseki K, Askenase P, Kanemitsu K
  • Organizer: International Congress of Immunology 2016
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2016-08-23
  • Int'l Joint Research
• [Presentation] 感染動物実験モデルによる、血流感染後2.5時間での臓器別バイオマーカーの検討 (2015)
  • Author(s): 山本夏男、阿部良伸、仲村 究、大花 昇、金光敬二
  • Organizer: 日本感染症学会東日本地方会総会学術集会
  • Place of Presentation: 東京ドームホテル
  • Year and Date: 2015-10-31
• [Presentation] カンジダ属の血流感染時に宿主抵抗性に関わるTh2に関連した因子の解析 (2015)
  • Author(s): 阿部良伸、山本夏男、仲村 究、大花 昇、伊関 憲、金光敬二
  • Organizer: 日本感染症学会東日本地方会総会学術集会
  • Place of Presentation: 東京ドームホテル
  • Year and Date: 2015-10-31
• [Presentation] A群溶連菌(GAS)由来の30K蛋白産物がIL-6及びNALP3の早期反応系に及ぼす役割 (2015)
  • Author(s): 山本夏男、新井和明、仲村 究、阿部良伸、吉田春乃、大花 昇、高橋 孝、金光敬二
  • Organizer: 日本感染症学会
  • Place of Presentation: ロイトン札幌 （札幌市）
  • Year and Date: 2015-10-23
• [Presentation] A群溶連菌(GAS)由来の低分子産物に応答する宿主細胞の分子機構 (2015)
  • Author(s): 山本夏男、新井和明、吉田春乃、阿部良伸、仲村 究、大橋一孝、大花 昇、高橋 孝、金光敬二
  • Organizer: 第６９回日本細菌学会 東北支部総会
  • Place of Presentation: 郡山ビッグパレット （福島）
  • Year and Date: 2015-08-22
• [Presentation] Natsuo Yamamoto, Takeshi Machida, Yuko Suzuki, Hideharu Sekine, Keiji Kanemitsu (2014)
  • Author(s): Elevated splenic Blimp-1 and CD14 of blood leukocytes within hours in IL-13 deficient mice sepsis
  • Organizer: The 41th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2014-12-12
• [Presentation] , Innate protective responses of B1 cells dependent on activation-induced cytidine deaminase (AID) and interleukin-13 (2013)
  • Author(s): Yamamoto N, Nakazawa N, Steven MK, DelaCruz C,Ohana N, Askenase PW, Kanemitsu K
  • Organizer: 15th International Congress of Immunology, Milan, Italy
  • Place of Presentation: Milan, Italy
• [Book] Sepsis (2016)
  • Author(s): Yamamoto N, Nakamura K, Kanemitsu K
  • Total Pages: 8
  • Publisher: SM journal
• [Remarks] 福島県立医科大学研究者データベース
  • URL: http://www.fmu.ac.jp/kenkyu/Profiles/39/0003823/profile.html
• [Remarks] Philip William Askenase, Yale University
  • URL: http://medicine.yale.edu/intmed/people/philip_askenase-2.profile
• [Remarks] 福島県立医科大学 研究者プロフィール
  • URL: http://www.fmu.ac.jp/kenkyu/Profiles/39/0003823/profile.html
• [Remarks] Allergy and Clinical Immunology , Yale University
  • URL: http://medicine.yale.edu/intmed/allergy/people/philip_askenase.profile
• [Remarks] Allergy and Clinical Immunology, Yale University
  • URL: http://medicine.yale.edu/intmed/allergy/people/philip_askenase.profile
• [Remarks] 医学部医学科 感染制御医学講座、福島医科大学研究者データベース
  • URL: http://www.fmu.ac.jp/kenkyu/Profiles/39/0003823/profile.html