Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection.
Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection.
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DOI：
10.3390/v13102055
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发表时间：
2021-10-13
期刊：
影响因子：
--
通讯作者：
Berdnikovs S
中科院分区：
文献类型：
--
作者：
Connelly AR;Jeong BM;Coden ME;Cao JY;Chirkova T;Rosas-Salazar C;Cephus JY;Anderson LJ;Newcomb DC;Hartert TV;Berdnikovs S
呼吸道合胞病毒(RSV)是一种季节性的粘膜病原体，感染纤毛呼吸道上皮，导致出生前六个月最严重的发病率。呼吸道合胞病毒是婴儿期急性呼吸道感染的常见原因，也是与哮喘发展密切相关的重要早期风险因素。虽然这种联系已被反复证明，但在人类对婴儿呼吸道合胞病毒感染对呼吸道上皮功能障碍的贡献的机制理解方面取得的进展有限。呼吸道合胞病毒在体外对呼吸道上皮细胞的活跃感染导致中枢代谢增强和整体高代谢状态；然而，在体内自然感染呼吸道合胞病毒是否会导致婴儿时期呼吸道上皮细胞持续的代谢重新编程，目前尚不清楚。为了解决这一差距，我们对2-3岁婴儿的鼻呼吸道上皮细胞(NAECs)进行了功能代谢组学、13C葡萄糖代谢通量分析和RNA-seq基因表达分析，这些细胞在出生第一年是否有RSV感染。我们发现，婴儿期RSV感染与持久的上皮代谢重编程有关，其特征是：(1)上皮细胞对葡萄糖的摄取和差异利用显著增加；(2)改变了对几种碳和能源的代谢偏好；(3)代谢参数出现明显的性别二型性，其中RSV诱导的代谢变化在男性上皮中最为明显。综上所述，我们的研究支持婴儿期RSV感染相关的上皮细胞代谢重编程现象，并为探索RSV诱导的早期生命上皮屏障功能障碍的机制开辟了令人兴奋的新场所。
Respiratory syncytial virus (RSV) is a seasonal mucosal pathogen that infects the ciliated respiratory epithelium and results in the most severe morbidity in the first six months of life. RSV is a common cause of acute respiratory infection during infancy and is an important early-life risk factor strongly associated with asthma development. While this association has been repeatedly demonstrated, limited progress has been made on the mechanistic understanding in humans of the contribution of infant RSV infection to airway epithelial dysfunction. An active infection of epithelial cells with RSV in vitro results in heightened central metabolism and overall hypermetabolic state; however, little is known about whether natural infection with RSV in vivo results in lasting metabolic reprogramming of the airway epithelium in infancy. To address this gap, we performed functional metabolomics, 13C glucose metabolic flux analysis, and RNA-seq gene expression analysis of nasal airway epithelial cells (NAECs) sampled from infants between 2–3 years of age, with RSV infection or not during the first year of life. We found that RSV infection in infancy was associated with lasting epithelial metabolic reprogramming, which was characterized by (1) significant increase in glucose uptake and differential utilization of glucose by epithelium; (2) altered preferences for metabolism of several carbon and energy sources; and (3) significant sexual dimorphism in metabolic parameters, with RSV-induced metabolic changes most pronounced in male epithelium. In summary, our study supports the proposed phenomenon of metabolic reprogramming of epithelial cells associated with RSV infection in infancy and opens exciting new venues for pursuing mechanisms of RSV-induced epithelial barrier dysfunction in early life.
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DOI：
10.1016/j.jaci.2017.04.010
发表时间：
2017-06
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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DOI：
10.1016/j.jaci.2016.01.006
发表时间：
2016-03
期刊：
The Journal of allergy and clinical immunology
影响因子：
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