复发性感染逐渐使宿主对肠道炎症的保护失效
Won Ho Yang1,2,3, Douglas M Heithoff1,3, Peter V Aziz1,2,3
1Center for Nanomedicine, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Science (New York, N.Y.)
|December 23, 2017
概括
反复发生的沙门氏菌 Typhimurium 感染会通过使保护性酸酶失效而导致持续的肠道炎症. 恢复性酸酶或抑制神经氨基酶为结肠炎提供治疗潜力.
科学领域:
- 胃肠病学
- 免疫学
- 微生物学
背景情况:
- 肠道炎症是结肠炎和炎症性肠道疾病的标志,
- 沙门氏菌 (Typhimurium) 感染是食物中毒的常见原因,可以引起肠道炎症.
研究的目的:
- 研究ST感染导致持续性肠炎的机制.
- 鉴定受ST感染破坏的宿主保护机制.
- 探索ST诱导的肠炎的治疗策略.
主要方法:
- 在小鼠模型中诱导反复的非致命胃性ST感染.
- 评估肠道炎症,病原体清除和疾病严重程度.
- 对宿主保护机制的分析,包括肠道性酸酶 (IAP) 活性和托尔类受体4 (TLR4) 信号.
- 用IAP或神经胺酶抑制剂进行治疗的评估.
主要成果:
- 复发性ST感染导致持续和升级的肠道炎症,主要是结肠,即使在病原体清除后.
- ST感染诱导了内源性神经氨基酶活性,加速了关键的保护酶IAP的脱离和清除.
- 疾病进展与TLR4激活有关,这是由于IAP基质脂多糖酸盐的积累.
- 通过保持IAP的丰富性和功能,IAP或神经胺基酶抑制剂Zanamivir可以改善疾病.
结论:
- ST感染破坏了涉及IAP的关键宿主防御机制,导致慢性肠炎.
- 在ST诱导大肠炎的发病过程中,TLR4介导的IAP脱离是关键途径.
- 恢复IAP水平或抑制神经氨基酶活性是炎症性肠道疾病的一种有前途的治疗方法.
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