TY  - JOUR
AU  - Magalhães, Vladimir G
AU  - Lukassen, Sören
AU  - Drechsler, Maike
AU  - Loske, Jennifer
AU  - Burkart, Sandy
AU  - Wüst, Sandra
AU  - Jacobsen, Eva-Maria
AU  - Röhmel, Jobst
AU  - Mall, Marcus A
AU  - Debatin, Klaus-Michael
AU  - Eils, Roland
AU  - Autenrieth, Stella
AU  - Janda, Aleš
AU  - Lehmann, Irina
AU  - Binder, Marco
TI  - Immune-epithelial cell cross-talk enhances antiviral responsiveness to SARS-CoV-2 in children.
JO  - EMBO reports
VL  - 24
IS  - 12
SN  - 1469-221X
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - DKFZ-2023-02047
SP  - e57912
PY  - 2023
N1  - 2023 Dec 6;24(12):e57912 / #EA:F170#LA:F170#
AB  - 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.
KW  - RIG-I like receptors (Other)
KW  - SARS-CoV-2 (Other)
KW  - age-dependence of disease (Other)
KW  - children (Other)
KW  - interferon response (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37818799
DO  - DOI:10.15252/embr.202357912
UR  - https://inrepo02.dkfz.de/record/284644
ER  -