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000284644 1001_ $$00000-0002-4593-3467$$aMagalhães, Vladimir G$$b0$$eFirst author
000284644 245__ $$aImmune-epithelial cell cross-talk enhances antiviral responsiveness to SARS-CoV-2 in children.
000284644 260__ $$aHoboken, NJ [u.a.]$$bWiley$$c2023
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000284644 520__ $$aThe risk of developing severe COVID-19 rises dramatically with age. Schoolchildren are significantly less likely than older people to die from SARS-CoV-2 infection, but the molecular mechanisms underlying this age-dependence are unknown. In primary infections, innate immunity is critical due to the lack of immune memory. Children, in particular, have a significantly stronger interferon response due to a primed state of their airway epithelium. In single-cell transcriptomes of nasal turbinates, we find increased frequencies of immune cells and stronger cytokine-mediated interactions with epithelial cells, resulting in increased epithelial expression of viral sensors (RIG-I, MDA5) via IRF1. In vitro, adolescent peripheral blood mononuclear cells produce more cytokines, priming A549 cells for stronger interferon responses to SARS-CoV-2. Taken together, our findings suggest that increased numbers of immune cells in the airways of children and enhanced cytokine-based interactions with epithelial cells tune the setpoint of the epithelial antiviral system. Our findings shed light on the molecular basis of children's remarkable resistance to COVID-19 and may suggest a novel concept for immunoprophylactic treatments.
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000284644 650_7 $$2Other$$aRIG-I like receptors
000284644 650_7 $$2Other$$aSARS-CoV-2
000284644 650_7 $$2Other$$aage-dependence of disease
000284644 650_7 $$2Other$$achildren
000284644 650_7 $$2Other$$ainterferon response
000284644 7001_ $$aLukassen, Sören$$b1
000284644 7001_ $$0P:(DE-He78)a931c8f45b0ade8be06a288982035fe3$$aDrechsler, Maike$$b2$$udkfz
000284644 7001_ $$aLoske, Jennifer$$b3
000284644 7001_ $$0P:(DE-He78)72f5852dfc0494f28b35adabf44cacef$$aBurkart, Sandy$$b4
000284644 7001_ $$0P:(DE-He78)06a6077b0cfcb0f4890fb5f2543c43be$$aWüst, Sandra$$b5$$udkfz
000284644 7001_ $$00000-0003-4750-0136$$aJacobsen, Eva-Maria$$b6
000284644 7001_ $$aRöhmel, Jobst$$b7
000284644 7001_ $$00000-0002-4057-2199$$aMall, Marcus A$$b8
000284644 7001_ $$aDebatin, Klaus-Michael$$b9
000284644 7001_ $$aEils, Roland$$b10
000284644 7001_ $$0P:(DE-He78)d3dbba28fe1239effd15962787cbc363$$aAutenrieth, Stella$$b11$$udkfz
000284644 7001_ $$00000-0001-5604-8378$$aJanda, Aleš$$b12
000284644 7001_ $$aLehmann, Irina$$b13
000284644 7001_ $$0P:(DE-He78)2fb2bd9048a3777dddc4cb89b115c187$$aBinder, Marco$$b14$$eLast author$$udkfz
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