%0 Journal Article
%A Magalhães, Vladimir G
%A Lukassen, Sören
%A Drechsler, Maike
%A Loske, Jennifer
%A Burkart, Sandy
%A Wüst, Sandra
%A Jacobsen, Eva-Maria
%A Röhmel, Jobst
%A Mall, Marcus A
%A Debatin, Klaus-Michael
%A Eils, Roland
%A Autenrieth, Stella
%A Janda, Aleš
%A Lehmann, Irina
%A Binder, Marco
%T Immune-epithelial cell cross-talk enhances antiviral responsiveness to SARS-CoV-2 in children.
%J EMBO reports
%V 24
%N 12
%@ 1469-221X
%C Hoboken, NJ [u.a.]
%I Wiley
%M DKFZ-2023-02047
%P e57912
%D 2023
%Z 2023 Dec 6;24(12):e57912 / #EA:F170#LA:F170#
%X 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.
%K RIG-I like receptors (Other)
%K SARS-CoV-2 (Other)
%K age-dependence of disease (Other)
%K children (Other)
%K interferon response (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37818799
%R 10.15252/embr.202357912
%U https://inrepo02.dkfz.de/record/284644