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Immune-epithelial cell cross‐talk enhances antiviral responsiveness to SARS‐CoV‐2 in children

The risk of developing severe COVID‐19 rises dramatically with age. Schoolchildren are significantly less likely than older people to die from SARS‐CoV‐2 infection, but the molecular mechanisms underlying this age‐dependence are unknown. In primary infections, innate immunity is critical due to the...

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Hauptverfasser: Gonçalves Magalhães, Vladimir (VerfasserIn) , Lukassen, Sören (VerfasserIn) , Drechsler, Maike (VerfasserIn) , Loske, Jennifer (VerfasserIn) , Burkart, Sandy S (VerfasserIn) , Wüst, Sandra (VerfasserIn) , Jacobsen, Eva‐Maria (VerfasserIn) , Röhmel, Jobst (VerfasserIn) , Mall, Marcus A (VerfasserIn) , Debatin, Klaus‐Michael (VerfasserIn) , Eils, Roland (VerfasserIn) , Autenrieth, Stella (VerfasserIn) , Janda, Aleš (VerfasserIn) , Lehmann, Irina (VerfasserIn) , Binder, Marco (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: December 06, 2023
In: EMBO reports
Year: 2023, Jahrgang: 24, Heft: 12, Pages: 1-20
ISSN:1469-3178
DOI:10.15252/embr.202357912
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.15252/embr.202357912
Verlag, kostenfrei, Volltext: https://www.embopress.org/doi/full/10.15252/embr.202357912
Volltext
Verfasserangaben:Vladimir G Magalhães, Sören Lukassen, Maike Drechsler, Jennifer Loske, Sandy S Burkart, Sandra Wüst, Eva‐Maria Jacobsen, Jobst Röhmel, Marcus A Mall, Klaus‐Michael Debatin, Roland Eils, Stella Autenrieth, Aleš Janda, Irina Lehmann & Marco Binder
Beschreibung
Zusammenfassung:The risk of developing severe COVID‐19 rises dramatically with age. Schoolchildren are significantly less likely than older people to die from SARS‐CoV‐2 infection, but the molecular mechanisms underlying this age‐dependence are unknown. In primary infections, innate immunity is critical due to the lack of immune memory. Children, in particular, have a significantly stronger interferon response due to a primed state of their airway epithelium. In single‐cell transcriptomes of nasal turbinates, we find increased frequencies of immune cells and stronger cytokine‐mediated interactions with epithelial cells, resulting in increased epithelial expression of viral sensors (RIG‐I, MDA5) via IRF1. In vitro, adolescent peripheral blood mononuclear cells produce more cytokines, priming A549 cells for stronger interferon responses to SARS‐CoV‐2. Taken together, our findings suggest that increased numbers of immune cells in the airways of children and enhanced cytokine‐based interactions with epithelial cells tune the setpoint of the epithelial antiviral system. Our findings shed light on the molecular basis of children's remarkable resistance to COVID‐19 and may suggest a novel concept for immunoprophylactic treatments.
Beschreibung:Online veröffentlicht: 11. Oktober 2023
Gesehen am 19.01.2024
Beschreibung:Online Resource
ISSN:1469-3178
DOI:10.15252/embr.202357912

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