Infant-derived human nasal organoids exhibit relatively increased susceptibility, epithelial responses, and cytotoxicity during RSV infection

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection Pub Date : 2024-10-09 DOI:10.1016/j.jinf.2024.106305

Gina M. Aloisio , Divya Nagaraj , Ashley M. Murray , Emily M. Schultz , Trevor McBride , Letisha Aideyan , Erin G. Nicholson , David Henke , Laura Ferlic-Stark , Anubama Rajan , Amal Kambal , Hannah L. Johnson , Elina Mosa , Fabio Stossi , Sarah E. Blutt , Pedro A. Piedra , Vasanthi Avadhanula

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引用次数: 0

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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在 RSV 感染期间，源自婴儿的人鼻腔器官组织显示出相对增加的易感性、上皮反应和细胞毒性。

背景：呼吸道合胞病毒（RSV）会导致严重的发病率和死亡率，尤其是在幼儿中。与健康成人相比，儿童感染 RSV 后病情更为严重的原因尚不完全清楚：方法：我们使用来自婴儿和成人的体外人类鼻腔类器官平台，研究在 RSV 复制的初始部位--鼻腔上皮--造成这种疾病差异的潜在机制：结果：婴儿来源的人鼻腔类器官-空气-液体界面（HNO-ALIs）系更容易受到早期RSV复制的影响。此外，与成人相比，婴儿来源的 HNO-ALIs 在统计学上显著引起更大的整体细胞因子反应、更多的粘液分泌和更大的细胞损伤。此外，成人的细胞因子反应与卓越的调节性细胞因子反应有关，这也是细胞损伤少于婴儿的原因：我们的数据凸显了婴儿和成人上呼吸道上皮细胞在细胞水平上对 RSV 感染反应的巨大差异。上皮细胞反应的这些差异可能会导致粘膜纤毛清除功能受损，先天免疫反应失调，从而使婴儿比成人更容易感染更严重的 RSV。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Infection 医学-传染病学

CiteScore

45.90

自引率

3.20%

发文量

475

审稿时长

16 days

期刊介绍： The Journal of Infection publishes original papers on all aspects of infection - clinical, microbiological and epidemiological. The Journal seeks to bring together knowledge from all specialties involved in infection research and clinical practice, and present the best work in the ever-changing field of infection. Each issue brings you Editorials that describe current or controversial topics of interest, high quality Reviews to keep you in touch with the latest developments in specific fields of interest, an Epidemiology section reporting studies in the hospital and the general community, and a lively correspondence section.