Infant-Derived Human Nasal Organoids Exhibit Relatively Increased Susceptibility, Epithelial Responses, and Cytotoxicity During RSV Infection

Authors

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

Language

English

Publication Date

12-1-2024

Journal

Journal of Infection

DOI

10.1016/j.jinf.2024.106305

PMID

39389204

PMCID

PMC12067953

PubMedCentral® Posted Date

5-12-2025

PubMedCentral® Full Text Version

Author MSS

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.

Keywords

Humans, Respiratory Syncytial Virus Infections, Organoids, Infant, Nasal Mucosa, Respiratory Syncytial Virus, Human, Cytokines, Adult, Virus Replication, Immunity, Innate, Disease Susceptibility, Epithelial Cells, Female, Male, RSV, Nasal organoids, infant, adult, infection, replication, innate immune responses

Published Open-Access

yes

Recommended Citation

Aloisio, Gina M; Nagaraj, Divya; Murray, Ashley M; et al., "Infant-Derived Human Nasal Organoids Exhibit Relatively Increased Susceptibility, Epithelial Responses, and Cytotoxicity During RSV Infection" (2024). Faculty and Staff Publications. 4824.
https://digitalcommons.library.tmc.edu/baylor_docs/4824