Aloisio Gina M, Nagaraj Divya, Murray Ashley M, Schultz Emily M, McBride Trevor, Aideyan Letisha, Nicholson Erin G, Henke David, Ferlic-Stark Laura, Rajan Anubama, Kambal Amal, Johnson Hannah L, Mosa Elina, Stossi Fabio, Blutt Sarah E, Piedra Pedro A, Avadhanula Vasanthi
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
J Infect. 2024 Dec;89(6):106305. doi: 10.1016/j.jinf.2024.106305. Epub 2024 Oct 9.
Respiratory syncytial virus (RSV) causes significant morbidity and mortality, especially in young children. Why RSV infection in children is more severe compared to healthy adults is not fully understood.
We used ex-vivo human nasal organoid platforms from infants and adults to investigate the underlying mechanism of this disease disparity at the initial site of RSV replication, the nasal epithelium.
Infant-derived human nasal organoid-air liquid interface (HNO-ALIs) lines were more susceptible to early RSV replication. Moreover, infant-derived HNO-ALIs elicited a statistically significant greater overall cytokine response, enhanced mucous production, and greater cellular damage compared to their adult counterparts. Furthermore, the adult cytokine response was associated with a superior regulatory cytokine response, which could explain less cellular damage than in infant lines.
Our data highlights substantial differences in how infant and adult upper respiratory tract epithelium responds to RSV infection at the cellular level. These differences in epithelial cellular response can lead to impaired mucociliary clearance, a more dysregulated innate immune response predisposing infants to more severe RSV infection compared to adults.
呼吸道合胞病毒（RSV）可导致严重的发病和死亡，尤其是在幼儿中。与健康成年人相比，儿童RSV感染为何更为严重尚未完全明确。
我们使用来自婴儿和成人的体外人鼻类器官平台，在RSV复制的起始部位——鼻上皮，研究这种疾病差异的潜在机制。
源自婴儿的人鼻类器官气液界面（HNO-ALI）细胞系对RSV早期复制更敏感。此外，与源自成人的HNO-ALI细胞系相比，源自婴儿的HNO-ALI细胞系引发的总体细胞因子反应在统计学上显著更强，黏液分泌增加，细胞损伤更严重。此外，成人的细胞因子反应与更强的调节性细胞因子反应相关，这可以解释其细胞损伤比婴儿细胞系更少的原因。
我们的数据突出了婴儿和成人上呼吸道上皮细胞在细胞水平上对RSV感染反应的显著差异。上皮细胞反应的这些差异可导致黏液纤毛清除功能受损，先天免疫反应失调更严重，使婴儿比成人更容易发生严重的RSV感染。
