Studies on new host-pathogen interaction via bacterial protease

• Project/Area Number: 15K15131
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Bacteriology (including mycology)
• Research Institution: Osaka University
• Principal Investigator: Arase Hisashi 大阪大学, 微生物病研究所, 教授 (10261900)
• Co-Investigator(Renkei-kenkyūsha): HIRAYASU Kouyuki 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (30585170) ; KATAYAMA Ichiro 大阪大学, 医学系研究科, 教授 (80191980)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: プロテアーゼ / LILRA2 / 免疫逃避 / 生体防御 / レジオネラ / マイコプラズマ

Outline of Final Research Achievements

Certain bacteria inactivate antibody by cutting variable region of antibody. Furthermore, we found that such truncated antibodies are recognized by immune activating receptor, LILRA2. Truncated antibodies specifically activated neutrophils expressing LILRA2. In addition, growth of Legionella in monocytes were suppressed by stimulation with truncated antibodies. These results suggested that LILRA2 plays an important role in host defense by recognizing truncated antibodies.

Research Products

• [Int'l Joint Research] Washington Univ. Sch. of Med., St Louis(米国)
• [Journal Article] LILRA2 is an innate immune sensor for microbially cleaved immunoglobulins. (2016)
  • Author(s): Hirayasu K, Saito F, Suenaga T, Shida K, Arase N, Oikawa K, Yamaoka T, Murota H, Chibana H, Nagai H, Nakamura Y, Katayama I, Colonna M, Arase H.
  • Journal Title: Nature Microbiology Volume: - Issue: 6 Pages: 1-7
  • DOI: 10.1038/nmicrobiol.2016.54
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Monocyte infiltration into obese and fibrilized tissues is regulated by PILRα. (2016)
  • Author(s): Kohyama M, Matsuoka S, Shida K, Sugihara F, Aoshi T, Kishida K, Ishii KJ, Arase H.
  • Journal Title: Eur J Immunol. Volume: in press Issue: 5 Pages: 1214-1223
  • DOI: 10.1002/eji.201545897
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Rheumatoid Rescue of Misfolded Cellular Proteins by MHC Class II Molecules: A New Hypothesis for Autoimmune Diseases. (2015)
  • Author(s): Arase H.
  • Journal Title: Adv. Immunol. Volume: 129 Pages: 1-23
  • DOI: 10.1016/bs.ai.2015.09.005
  • ISBN: 9780128047996
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cellular misfolded proteins rescued from degradation by MHC class II molecules are possible targets for autoimmune diseases. (2015)
  • Author(s): Arase N, Arase H.
  • Journal Title: J Biochem. Volume: 158 Issue: 5 Pages: 367-372
  • DOI: 10.1093/jb/mvv093
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Sialic Acids on Varicella-Zoster Virus Glycoprotein B Are Required for Cell-Cell Fusion. (2015)
  • Author(s): Suenaga T, Matsumoto M, Arisawa F, Kohyama M, Hirayasu K, Mori Y, Arase H.
  • Journal Title: J Biol Chem. Volume: 290 Issue: 32 Pages: 19833-19843
  • DOI: 10.1074/jbc.m114.635508
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Functional and genetic diversity of leukocyte immunoglobulin-like receptor and implication for disease associations. (2015)
  • Author(s): Hirayasu K, Arase H.
  • Journal Title: J Hum Genet. Volume: 60 Issue: 11 Pages: 703-708
  • DOI: 10.1038/jhg.2015.64
  • NAID: 40020655165
  • Peer Reviewed
• [Presentation] Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2 (2016)
  • Author(s): Kouyuki Hirayasu, Fumiji Saito, Tadahiro Suenaga, Kyoko Shida, Noriko Arase, Keita Oikawa, ToshifumiYamaoka, Hiroyuki Murota, Hiroji Chibana, Ichiro Nakagawa, Tomoko Kubori, Hiroki Nagai, Yuji Nakamaru, Ichiro Katayama, Marco Colonna, Hisashi Arase
  • Organizer: 第45日本免疫学会学術集会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄）
  • Year and Date: 2016-12-05
• [Presentation] HLA クラス I 認識受容体群 LILR の新展開 - 病原微生物によって壊された抗体を認識 する生体防御機構 - (2016)
  • Author(s): 平安 恒幸, 齋藤 史路, 末永 忠広, 信田 京子, 荒瀬 規子, 及川 敬太, 山岡 俊文, 室田 浩之, 知花 博治, 中川 一路, 久堀 智子, 永井 宏樹, 中丸 裕爾, 片山 一朗, Marco Colonna, 荒瀬 尚
  • Organizer: 第25回日本組織適合性学会大会
  • Place of Presentation: 北海道大学（北海道）
  • Year and Date: 2016-12-05
• [Presentation] Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2 (2016)
  • Author(s): Hirayasu K, Saito F, Suenaga T, Shida K, Arase N, Oikawa K, Yamaoka T, Murota H, Chibana H, Nakagawa I, Kubori T, Nagai H, Nakamaru Y, Katayama I, Colonna M, Arase H
  • Organizer: 16th Annual Meeting of the Society for Natural Immunity
  • Place of Presentation: Taormina, Italy
  • Year and Date: 2016-10-02
  • Int'l Joint Research
• [Presentation] Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2 (2016)
  • Author(s): Hirayasu K, Saito F, Suenaga T, Shida K, Arase N, Oikawa K, Yamaoka T, Murota H, Chibana H, Nakagawa I, Kubori T, Nagai H, Nakamaru Y, Katayama I, Colonna M, Arase H
  • Organizer: 15th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Away Island, Japan
  • Year and Date: 2016-09-06
  • Int'l Joint Research
• [Presentation] DIR is an innate immune sensor for microbially cleaved immunoglobulins (2015)
  • Author(s): Hirayasu Kouyuki, Saito Fumiji, Suenaga Tadahiro, Shida Kyoko, Arase Noriko, Oikawa Keita, Yamaoka Toshifumi, Murota Hiroyuki, Chibana Hiroji, Nagai Hiroki, Nakamaru Yuji, Katayama Ichiro, Arase Hisashi
  • Organizer: 第44日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道）
  • Year and Date: 2015-11-18
• [Remarks] 大阪大学微生物病研究所免疫化学分野ホームページ
  • URL: http://immchem.biken.osaka-u.ac.jp
• [Remarks]
  • URL: http://immchem.biken.osaka-u.ac.jp