在沙门氏菌系统性感染中,炎症酶激活和热死介导凝血病和炎症
Ankit Pandeya1, Yan Zhang2, Jian Cui3
1Department of Pharmaceutical Sciences, Irma Lerma Rangel School of Pharmacy, Texas A&M University, College Station, TX, USA; Department of Chemistry, University of Kentucky, Lexington, KY, USA.
Microbiological research
|July 19, 2023
概括
炎症酶激活关键驱动沙门氏菌系统性感染和凝血病. 使用炎症酶抑制剂阻断caspase-1或gasdermin-D (GSDMD) 改善了生存率,并防止了感染期间的血液凝固.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 病变的发生和发病.
背景情况:
- 炎症酶激活是对抗细菌病原体的关键免疫反应.
- 虽然在口腔沙门氏菌感染中具有保护作用,但其在全身感染中的作用不太清楚.
研究的目的:
- 研究炎症酶激活在系统性沙门氏菌感染病原发生中的作用.
- 为了确定与沙门氏菌诱导的凝血病相关的炎症性通路.
主要方法:
- 系统感染模型使用小鼠内注射沙门氏菌.
- 评估生存,促炎性细胞因子水平 (IL-1β,IL-6,TNFα) 和凝血参数 (前热血素时间,热血素-抗热血素复合体).
- 对具有炎酶缺陷的小鼠 (caspase-1,gasdermin-D) 和缺乏特定毒性因子 (flagellin,SPI1) 的沙门氏菌突变物的评估.
主要成果:
- 缺乏caspase-1或gasdermin-D的小鼠表现出延长生存时间和减少全身炎症.
- 这些缺陷对沙门氏菌诱导的凝血病有保护作用,通过正常化的前热血素时间和热血素-抗热血素水平来表明这一点.
- 通过鞭毛素和SPI1激活NAIP/NLRC4炎症酶,有助于凝血病.
- 即使没有鞭毛素和SPI1,沙门氏菌也通过caspase-11/NLRP3途径触发了凝血病.
结论:
- 炎症酶激活和热死在系统性沙门氏菌感染的发病过程中起着重要作用.
- 针对包括caspase-1,GSDMD和下游细胞因子在内的炎症体通路,提供了针对严重的沙门氏菌感染和相关凝血病的潜在治疗策略.
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