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@ARTICLE{Magalhes:284644,
author = {V. G. Magalhães$^*$ and S. Lukassen and M. Drechsler$^*$
and J. Loske and S. Burkart$^*$ and S. Wüst$^*$ and E.-M.
Jacobsen and J. Röhmel and M. A. Mall and K.-M. Debatin and
R. Eils and S. Autenrieth$^*$ and A. Janda and I. Lehmann
and M. Binder$^*$},
title = {{I}mmune-epithelial cell cross-talk enhances antiviral
responsiveness to {SARS}-{C}o{V}-2 in children.},
journal = {EMBO reports},
volume = {24},
number = {12},
issn = {1469-221X},
address = {Hoboken, NJ [u.a.]},
publisher = {Wiley},
reportid = {DKFZ-2023-02047},
pages = {e57912},
year = {2023},
note = {2023 Dec 6;24(12):e57912 / #EA:F170#LA:F170#},
abstract = {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.},
keywords = {RIG-I like receptors (Other) / SARS-CoV-2 (Other) /
age-dependence of disease (Other) / children (Other) /
interferon response (Other)},
cin = {F170 / F171},
ddc = {570},
cid = {I:(DE-He78)F170-20160331 / I:(DE-He78)F171-20160331},
pnm = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
pid = {G:(DE-HGF)POF4-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37818799},
doi = {10.15252/embr.202357912},
url = {https://inrepo02.dkfz.de/record/284644},
}