多种细菌的细胞内大分子塑造上呼吸道上皮细胞的单细胞炎症特征。

Polybacterial intracellular macromolecules shape single-cell inflammatory profiles in upper airway epithelia.

作者信息

Easter Quinn T, Alvarado-Martinez Zabdiel, Kunz Meik, Matuck Bruno F, Rupp Brittany T, Weaver Theresa, Ren Zhi, Tata Aleksandra, Caballero-Perez Juan, Oscarson Nick, Hasuike Akira, Ghodke Ameer N, Kimple Adam J, Tata Purushothama R, Randell Scott H, Koo Hyun, Ko Kang I, Byrd Kevin M

机构信息

Department of Oral and Craniofacial Molecular Biology, Philips Institute for Oral Health Research, Virginia Commonwealth University, Richmond, VA, USA.

Independent Contractor, Bethesda, MD, USA.

出版信息

NPJ Biofilms Microbiomes. 2025 Jun 10;11(1):100. doi: 10.1038/s41522-025-00735-5.

DOI:10.1038/s41522-025-00735-5

PMID:40494852

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12152179/

Abstract

Mucosal epithelial cells of the upper airways are continuously exposed to microbes throughout life. Specialized niches such as the anterior nares and the tooth are especially susceptible to dysbiosis and chronic inflammatory diseases. Here, we reanalyzed our v1-Human Periodontal Atlas, identifying polybacterial signatures (20% Gram-positive; 80% Gram-negative) and distinct responses of bacterial-associated epithelia. Fluorescence microscopy detected numerous persistent polybacterial intracellular macromolecules (PIMs) within human oral keratinocytes (HOKs), including bacterial rRNA, mRNA, and glycolipids. PIM levels directly correlated with enhanced receptor-ligand signaling in vivo. Inflammatory "keratokines" targeting immune cells were synergistically upregulated in lipopolysaccharide-challenged HOKs, while endogenous lipoteichoic acid (LTA) correlated with CXCL1/8 expression in vitro and in vivo. Application of Drug2Cell suggested altered drug efficacy predictions based on PIM detection-agnostic of disease state. CXCL1/8 expression again correlated with LTA in epithelial cells of the nasal cavity, oropharynx, and trachea. Thus, PIMs shape epithelial single-cell profiles across upper airway mucosae.

摘要

上呼吸道的黏膜上皮细胞在一生中持续暴露于微生物。诸如前鼻孔和牙齿等特殊生态位尤其易发生生态失调和慢性炎症性疾病。在此，我们重新分析了我们的v1-人类牙周图谱，确定了多菌特征（20%革兰氏阳性菌；80%革兰氏阴性菌）以及细菌相关上皮细胞的不同反应。荧光显微镜在人口腔角质形成细胞（HOKs）内检测到大量持续存在的多菌细胞内大分子（PIMs），包括细菌rRNA、mRNA和糖脂。PIM水平与体内增强的受体-配体信号传导直接相关。在脂多糖刺激的HOKs中，靶向免疫细胞的炎性“角质形成因子”协同上调，而内源性脂磷壁酸（LTA）在体外和体内均与CXCL1/8表达相关。Drug2Cell的应用表明，基于PIM检测的药物疗效预测发生了改变，与疾病状态无关。CXCL1/8表达在鼻腔、口咽和气管的上皮细胞中再次与LTA相关。因此，PIMs塑造了上呼吸道黏膜上皮单细胞图谱。