幽門螺旋桿菌鞭毛在宿主免疫反應之角色

Role of Helicobacter pylori flagella in mediating host immune responses

林忠誠(Chung-Cheng Lin)

指導教授 ： 張玲麗

高雄醫學大學/醫學院/醫學研究所碩士班/碩士(2017年)

摘要

中文摘要
背景:現今已知胃間質細胞(gastric stromal cells, GSCS)在癌微環境中扮演重要角色，但目前仍不清楚當幽門桿菌感染時、胃間質細胞是否影響樹突細胞之免疫反應?。因此本研究目的是探討幽門桿菌鞭毛、LPS等對胃間質細胞的影響以及是否影響樹突細胞分泌IL-10。
方法: 本實驗由幽門桿菌陰性的健康人周邊血分離白血球後以GM-CSF及IL-4誘發成樹突細胞(monocyte derived dendritic cells, MDDC)，胃間質細胞是由三位胃癌病患(T2、T9、T21)及一位胃炎患者(N1)之胃部組織分離培養。本研究取野生型幽門桿菌J99及其鞭毛突變型幽門桿菌株ΔcsrA、 ΔcsrA- revertant、ΔrpoN，或是幽門桿菌LPS突變菌株FutA、FutB、FutC感染胃基質細胞後再與樹突細胞共同培養24小時，隨後收集上清液，並藉ELISA偵測IL-10細胞激素分泌。
結果: 首先證實幽門桿菌感染之胃間質細胞會刺激MDDC分泌IL-10。鞭毛突變幽門桿菌(J99 ΔcsrA、J99 ΔcsrA-revertant和J99ΔrpoN)感染胃間質細胞刺激MDDC所分泌IL-10並沒有受到影響。取自胃癌(CA)與胃潰瘍(GU)病患所分離出之幽門桿菌的LPS感染的胃間質細胞則不會刺激MDDC分泌IL-10。
結論:幽門桿菌鞭毛與幽門桿菌LPS都是較弱抗原結構並不影響

關鍵字

幽門桿菌 ； 樹突細胞:胃間質細胞:鞭毛

並列摘要

Abstract
Background: It has been known that mucosal stromal cells represent a crucial component of the cancer microenvironment. The molecular mechanisms by which H. pylori infected gastric stromal cells and a subsequent response with DCs remain unclear. The current study was to investigate whether flagella and LPS of H. pylori will interact with the gastric stromal cells and influence the IL-10 secretion from DC.

Methods: In this study, peripheral blood mononuclear cells (PBMCs) were isolated from healthy individuals with no history of H. pylori infection. Then induced immature DCs in the presence of IL-4 and GM-CSF within 5–7 days. Gastric stromal cells were obtained from three gastric cancer patients (T21, T2, T9) and one gastritis patient (N1). H. pylori J99 and flagella mutant strains ΔcsrA、ΔcsrA- revertant、ΔrpoN, and LPS mutant strains FutA、FutB、FutC of H. pylori(26695) were used. Level of IL-10 secreted from DCs was measured when DCs were co-cultured with H. pylori-primed GSCs.

Results: Increased level of IL-10 secretion from DCs was found when DCs were co-cultured with Hp-primed GSCs. However, when flagella mutant strains of Hp (J99 ΔcsrA, J99 ΔcsrA-revertant and J99ΔrpoN) were used to stimulate GSCs, the IL-10 expression in DCs was not significantly difference with wild type strain J99. In addition, the DC-priming effect and IL-10 secretion was not different when LPS was obtained from gastric cancer (CA) or gastric ulcer (GU) patients.

Conclusion: Weak immunogenic antigens of Helicobacter flagella and LPS do not play roles in priming gastric stromal cells and effecting immune responses of DCs. Therefore, H. pylori can evade host immune responses, persist localize in the gastric mucosa and development of chronic gastric diseases.

並列關鍵字

Helicobacter pylori ； dendritic cell ； gastric stromal cell:flagella

參考文獻

參考資料(References

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