Helicobacter pylori cholesteryl alpha-glucosides contribute to immune response by natural killer T cells

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790388
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Ehime University
• Principal Investigator: ITO Yuki 愛媛大学, プロテオサイエンスセンター, 助教(特定教員) (10608334)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: ヘリコバクター・ピロリ / 臨床分離株 / 糖脂質 / インバリアントNKT細胞

Research Abstract

It has not been determined how cholesteryl alpha-glucosyltransferase (aCgT), which forms cholesteryl alpha-glucosides (aCGs), functions in the pathogenesis of H. pylori infection. We show that the activity of aCgT from H. pylori clinical isolates is highly correlated with the degree of gastric atrophy. We investigated the role of aCGs in various aspects of the immune response. aCGs were recognized by invariant natural killer T (iNKT) cells, eliciting an immune response in vitro and in vivo. Following inoculation of H. pylori harboring highly active aCgT into iNKT cell-deficient (Ja18 KO) or wild-type mice, bacterial recovery significantly increased in Ja18 KO compared to wild-type mice. Moreover, cytokine production characteristic of Th1 and Th2 cells dramatically decreased in Ja18 KO compared to wild-type mice. These findings demonstrate that aCGs play critical roles in H. pylori-mediated gastric inflammation and precancerous atrophic gastritis.

Research Products

• [Journal Article] Helicobacter pylori cholesterylα-glucosides contribute to its pathogenicity and immune response by natural killer T cells (2013)
  • Author(s): Ito Y, Vela JL, Matsumura F, Hoshino H, Tyznik A, Lee H, Girardi E, Zajonc DM, Liddington R, Kobayashi M, Bao X, Bugaytsova J, Boren T, Jin R, Zong Y, Seeberger PH, Nakayama J, Kronenberg M, and Fukuda M
  • Journal Title: PLoS One Volume: 8(* equal contribution) Pages: e78191
• [Presentation] ピロリ菌の持つコレステリル-α-グルコシド類の免疫学的機能 (2013)
  • Author(s): 伊藤有紀
  • Organizer: 新学術領域研究「自然炎症」「脂質マシナリー」合同若手ワークショップ
  • Place of Presentation: 徳島市
  • Year and Date: 2013-07-02
• [Presentation] Seeberger PH, Nakayama J, Kronenberg M, and Fukuda M. Helicobacter pylori cholesterylα-glucosides are critical for bacterial growth and activation of invariant NKT cells (2012)
  • Author(s): Ito Y, Vela JL, Matsumura F, Hoshino H, Tyzniz A, Lee H, Girardi E, Zajonc MD, Kobayash M, Bao X, Boren T
  • Organizer: Joint Meeting of the Society for Glycobiology and American Society for Matrix Biology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2012-11-12
• [Presentation] Pathological and immunological functions of cholesterylα-glucosides in Helicobacter pylori-associated inflammation (2012)
  • Author(s): Ito Y
  • Organizer: Gordon Research Conference (Glycolipid & Sphingolipid Biology)
  • Place of Presentation: Lucca, Italy
  • Year and Date: 2012-04-25