多细菌细胞内宏分子在上呼吸道上皮质中形成单细胞炎症特征
Quinn T Easter1, Zabdiel Alvarado-Martinez2, Meik Kunz3
1Department of Oral and Craniofacial Molecular Biology, Philips Institute for Oral Health Research, Virginia Commonwealth University, Richmond, VA, USA.
NPJ biofilms and microbiomes
|June 10, 2025
概括
在人类口腔角质细胞中发现了持久的多细菌细胞内宏分子 (PIM),影响了上呼吸道粘膜的免疫反应和药物疗效. 这些发现揭示了PIMs.
科学领域:
- 微生物学和免疫学
- 皮质细胞生物学 皮质细胞生物学
- 口腔和上呼吸道的健康状况
背景情况:
- 上呼吸道粘膜上皮细胞不断与微生物相互作用,像前鼻腔和牙这样的隙容易发生失生症和炎症.
- 以前的研究已经强调了特殊的粘膜部位对微生物失衡和慢性炎症状况的易感性.
研究的目的:
- 重新分析人类牙周地图,以确定多细菌特征和上皮反应.
- 研究人类口腔角质细胞 (HOKs) 中细胞内细菌大分子的存在和影响.
- 探索这些宏分子,免疫信号和药物疗效预测之间的相关性.
主要方法:
- 重新分析v1-人类牙周图谱数据集.
- 光显微镜检测HOKs中的多细菌细胞内宏分子 (PIMs).
- 在体外和体内对PIM水平与受体连接体信号传递,炎症标记物 (克拉托金,CXCL1/8),和脂铁醇酸 (LTA) 的相关性分析.
- 应用Drug2Cell用于改变药物疗效的预测.
主要成果:
- 识别了多种细菌的特征 (80%的格拉姆阴性,20%的格拉姆阳性) 和明显的上皮反应.
- 在HOC中检测到持久的PIMs (细菌rRNA,mRNA,甘油脂),与增强的体内受体-连接体信号相关.
- 在受脂多糖挑战的HOC中观察到炎症性角氨酸的协同上调.
- 在体外和体内发现了内源性脂肪酸 (LTA) 和CXCL1/8表达之间的相关性.
- 药物2细胞分析表明,PIM检测改变了药物的疗效预测,而不依赖于疾病状态.
- CXCL1/8表达与鼻腔,口腔和气管的上皮细胞中的LTA相关.
结论:
- 多细菌细胞内宏分子 (PIMs) 在上呼吸道上皮质细胞中普遍存在.
- PIMs显著影响上皮细胞信号传递,炎症反应和潜在的药物疗效.
- 这些发现突出了PIMs作为整个上呼吸道粘膜上皮质细胞配置的关键调节器.
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