在病毒感染中,Sirtuin 2通过NAD+合成途径调节中性粒细胞的功能
Zhiyuan Zhang1, Qiuli Yang1, Yingjie Dong1
1Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
iScience
|July 8, 2024
概括
通过调节中性粒细胞功能和NAD+代谢,SIRT2缺乏限制病毒感染. 这涉及增加林酸的产生,这支持免疫反应对呼吸道病毒.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 病毒学 病毒学
背景情况:
- 中性粒细胞对抗病毒免疫力至关重要,但其精确的作用和调节机制尚未完全理解.
- 急性呼吸道病毒感染引发了涉及中性粒细胞的复杂免疫反应,影响了疾病的严重程度.
研究的目的:
- 阐明SIRT2在病毒感染期间调节中性粒细胞功能的作用.
- 调查潜在的分子机制,特别关注NAD+代谢及其对中性粒细胞活动的影响.
主要方法:
- 使用了急性呼吸道病毒感染的小鼠模型.
- 评估了中性粒细胞透,细胞因子分泌和中性粒细胞外细胞陷 (NET) 的形成.
- 分析了参与NAD+和氨酸代谢的关键酶的表达,包括3-氨酸甲酸氧酶 (3-HAO) 和氨酸酸转移酶 (QPRT).
主要成果:
- 缺少SIRT2显著抑制了中性粒细胞透,炎症性细胞因子分泌和NET形成,从而改善了疾病症状.
- 缺少SIRT2可提高3-HAO和QPRT的调节,从而增强林酸 (QA) 的合成.
- 中性粒细胞衍生的QA作为补充细胞内NAD+池的替代来源,从而调节中性粒细胞的功能.
结论:
- 揭示了一种新的SIRT2依赖途径,通过QPRT介导的NAD+代谢调节中性粒细胞功能.
- 证明中性粒细胞衍生的QA可以被利用来补充NAD+池,影响抗病毒反应.
- 研究结果表明,在病毒感染中针对NAD+代谢进行免疫治疗的潜在治疗策略.
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