Infant-derived human nasal organoids exhibit relatively increased susceptibility, epithelial responses, and cytotoxicity during RSV infection - 06/12/24
, Vasanthi Avadhanula a, ⁎ Summary |
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.
Le texte complet de cet article est disponible en PDF.Highlights |
• | Infant-derived compared to adult-derived HNOs have more mucus production at baseline. |
• | During RSV infection, infants produce higher amounts of infectious virus over adults. |
• | Infant HNOs have a more robust cytokine response. |
• | RSV infection causes increased cellular damage in infants compared to adult HNOs. |
Keywords : RSV, Nasal organoids, Infant, Adult, Infection, Replication, Innate immune responses
Plan
Vol 89 - N° 6
Article 106305- décembre 2024 Retour au numéro
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