Marsico Lung Institute.
Department of Microbiology and Immunology.
J Clin Invest. 2024 Nov 1;134(21):e185689. doi: 10.1172/JCI185689.
Immature innate and adaptive immunity and vulnerability of narrower airways to obstruction increase the susceptibility of infants to severe respiratory syncytial virus (RSV) disease. In this issue of the JCI, Zhao et al. illustrated greater intrinsic susceptibility of pediatric versus adult airway epithelial cells to RSV-induced cytopathology. Using precision cut lung slices (PCLS) and air-liquid interface (ALI) airway epithelial cell cultures, the authors showed that impaired STAT3 activation in RSV-infected pediatric multiciliated cells increased cell apoptosis and viral shedding, which enhanced the spread of infection. Bolstering STAT3 activation and treatment of neonatal mice with apoptosis inhibitors suppressed virus spread, suggesting that enhancing STAT3 activation may provide therapeutic benefit.
未成熟的先天和适应性免疫以及更窄气道对阻塞的易感性增加了婴儿患严重呼吸道合胞病毒(RSV)疾病的易感性。在本期 JCI 中,Zhao 等人说明了儿科气道上皮细胞相对于成人气道上皮细胞对 RSV 诱导的细胞病变的固有易感性更大。使用精密切割肺切片(PCLS)和气液界面(ALI)气道上皮细胞培养物,作者表明 RSV 感染的儿科多纤毛细胞中 STAT3 激活受损会增加细胞凋亡和病毒脱落,从而增强感染的传播。增强 STAT3 激活并使用凋亡抑制剂治疗新生小鼠可抑制病毒传播,这表明增强 STAT3 激活可能提供治疗益处。