改变了对登革热病毒血清型三的中性粒细胞反应:通过稳定Mcl-1来调节延迟的亡
Chatcharin Kamsom1, Steven W Edwards1,2, Jiraphon Thaosing1
1Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Scientific reports
|August 8, 2024
概括
登革热病毒3型血清 (DV3) 延长了中性粒细胞的存活时间,并增强了它们的炎症功能. 这项研究揭示了DV3-激活的中性粒细胞如何通过延迟细胞死亡和促进炎症来促进登革热的发病.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 病理学 病理学 病理学
背景情况:
- 登革热病毒 (DV) 构成了重大的全球卫生挑战,影响疾病严重程度的宿主-病原体相互作用仍不明确.
- 中性粒细胞参与登革热的发病,但DV激活中性粒细胞的具体机制和功能特征尚未完全阐明.
研究的目的:
- 研究登革热病毒3型血清 (DV3) 对中性粒细胞寿命和功能的影响.
- 阐明DV诱导的中性粒细胞活化和生存的基础分子机制.
主要方法:
- 用DV3化中性粒细胞并测量细胞存活率,细胞亡标志物,活性氧物种 (ROS) 生成和细胞因子/化学因子表达.
- 在DV3治疗后分析基因和蛋白质表达,包括BCL-XL和Mcl-1.
- 对DV3激活中性粒细胞的迁移标记表达 (CCR7,CXCR4) 的评估.
主要成果:
- DV3显著延长了中性粒细胞的存活时间,在72小时后显著的细胞活力比率超过了单独GM-CSF和TNF-α的影响.
- 由DV3诱导的增强ROS生成和中性粒细胞增加IL-8和MCP-1 (CCL2) 的表达.
- DV3提高了BCL-XL和Mcl-1基因表达的调节,并促进了Mcl-1蛋白稳定,类似于GM-CSF,同时也增加了迁移标记物CCR7和CXCR4的表达.
结论:
- DV3通过延迟亡促进中性粒细胞的存活,并增强促炎功能,包括ROS生产和细胞因子释放.
- 激活DV3的中性粒细胞可能通过延长存活时间和潜在的迁移到淋巴结导致登革热病理.
- 这些发现表明登革热激活的中性粒细胞在调节适应性免疫力方面的作用,为登革热疾病机制提供了新的见解.
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