The glycosphingolipid-mediated recognition of mycobacteria by human phagocytes

• Project/Area Number: 25860831
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Infectious disease medicine
• Research Institution: Juntendo University
• Principal Investigator: NAKAYAMA Hitoshi 順天堂大学, 医療看護学部, 助教 (70514933)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 病原性抗酸菌 / リポアラビノマンナン / 好中球 / ラクトシルセラミド / 貪食 / 食胞成熟阻害 / 食胞成熟 / 抗酸菌

Outline of Final Research Achievements

Pathogenic mycobacteria such as Mycobacterium tuberculosis cause phagosomal maturation (phagosome-lysosome fusion) arrest. In this study, we aimed to elucidate the mechanism of glycosphingolipid-mediated mycobacterial recognition. Our results showed that mycobacterial LAM bound to lactosylceramide (LacCer), and affected LacCer-mediated phagosomal maturation in human neutrophils. These results provide new insights into how pathogenic mycobacteria inhibit phagosome-lysosome fusion.

Research Products

• [Journal Article] Properties and functions of lactosylceramide from mouse neutrophils (2015)
  • Author(s): Iwabuchi K, Masuda H, Kaga N, Nakayama H, Matsumoto R, Iwahara C, Yoshizaki F, Tamaki Y, Kobayashi T, Hayakawa T, Ishii K, Yanagida M, Ogawa H, Takamori K
  • Journal Title: Glycobiology Volume: 25 Issue: 6 Pages: 655-668
  • DOI: 10.1093/glycob/cwv008
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Direct interaction, instrumental for signaling processes, between LacCer and Lyn in the lipid rafts of neutrophil-like cells. (2015)
  • Author(s): Chiricozzi E, Ciampa MG, Brasile G, Compostella F, Prinetti A, Nakayama H, Ekyalongo RC, Iwabuchi K, Sonnino S, Mauri L
  • Journal Title: Journal of Lipid Research Volume: 56 Issue: 1 Pages: 129-41
  • DOI: 10.1194/jlr.m055319
  • Peer Reviewed
• [Journal Article] Organization and functions of glycolipid-enriched microdomains in phagocytes. (2015)
  • Author(s): Ekyalongo RC, Nakayama H, Kina K, Kaga N, Iwabuchi K
  • Journal Title: Biochim Biophys Acta Volume: 1851 Issue: 1 Pages: 90-7
  • DOI: 10.1016/j.bbalip.2014.06.009
  • Peer Reviewed
• [Journal Article] Glycosphingolipid-Receptor Interactions in the Innate Immune Responses. (2014)
  • Author(s): Nakayama H, Iwabuchi K
  • Journal Title: Glycoscience: Biology and Medicine Volume: Part VII Pages: 699-705
  • DOI: 10.1007/978-4-431-54836-2_141-1
  • ISBN: 9784431548362
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Pseudomonas-derived ceramidase induces production of inflammatory mediators from human keratinocytes via sphingosine-1-phosphate (2014)
  • Author(s): Oizumi A, Nakayama H, Okino N, Iwahara C, Kina K, Matsumoto R, Ogawa H, Takamori K, Ito M, Suga Y, Iwabuchi K.
  • Journal Title: PLoS One. Volume: 9(2) Issue: 2 Pages: 89402-89402
  • DOI: 10.1371/journal.pone.0089402
  • Peer Reviewed / Open Access
• [Presentation] Lactosylceramide mediates innate immune responses depending on PAMPs in human neutrophils. (2014)
  • Author(s): H. Nakayama and K. Iwabuchi
  • Organizer: Joint Meeting of the Society for Glycobiology (SFG) and the Japanese Society of Carbohydrate Research (JSCR)
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 2014-11-16 – 2014-11-21
• [Presentation] ヒト好中球におけるCD14 依存性LPS シグナルはラクトシルセラミドのマイクロドメインにより仲 介される (2014)
  • Author(s): 中山仁志, 玉木友樹, ルーディ チミンチ イキャロンゴ ボ ラウェレ, 岩渕和久
  • Organizer: 第7回セラミド研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-10-30 – 2014-10-31
• [Presentation] リポ多糖はヒト好中球におけるラクトシルセラミドを介したシグナル伝達機構を活性化する (2014)
  • Author(s): 中山仁志, 玉木友樹, ルーディ チミンチ イキャロンゴ ボ ラウェレ, 栗原秀剛, 岩渕和久
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] ラクトシルセラミドはヒト好中球の細胞膜上でLynと直接会合している (2013)
  • Author(s): 中山仁志, Elena Chiricozzi, Laura Mauri, Alessandro Prinetti, Sandro Sonnino, 岩渕和久
  • Organizer: 第32回日本糖質学会年会
  • Place of Presentation: 大阪国際交流センター
• [Presentation] ヒトマクロファージにおけるラクトシルセラミドの役割について (2013)
  • Author(s): 中山仁志, 栗原秀剛, 髙森建二, 小川秀興, 岩渕和久
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜