tetano
Editor, Senior Moderator
Nat Biotechnol
. 2021 Aug 18.
doi: 10.1038/s41587-021-01037-9. Online ahead of print.
Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children
J Loske[SUP] #[/SUP][SUP] 1 [/SUP], J Röhmel[SUP] #[/SUP][SUP] 2 [/SUP], S Lukassen[SUP] #[/SUP][SUP] 3 [/SUP], S Stricker[SUP] 2 [/SUP], V G Magalhães[SUP] 4 [/SUP], J Liebig[SUP] 3 [/SUP], R L Chua[SUP] 3 [/SUP], L Thürmann[SUP] 1 [/SUP], M Messingschlager[SUP] 1 [/SUP], A Seegebarth[SUP] 1 [/SUP], B Timmermann[SUP] 5 [/SUP], S Klages[SUP] 5 [/SUP], M Ralser[SUP] 6 [/SUP], B Sawitzki[SUP] 7 [/SUP], L E Sander[SUP] 8 9 [/SUP], V M Corman[SUP] 10 11 [/SUP], C Conrad[SUP] 3 [/SUP], S Laudi[SUP] 12 [/SUP], M Binder[SUP] 4 [/SUP], S Trump[SUP] 1 [/SUP], R Eils[SUP] 13 14 15 [/SUP], M A Mall[SUP] 2 9 [/SUP], I Lehmann[SUP] 1 9 16 [/SUP]
Affiliations
Abstract
Children have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and a substantially lower risk for developing severe coronavirus disease 2019 compared with adults. However, the molecular mechanisms underlying protection in younger age groups remain unknown. Here we characterize the single-cell transcriptional landscape in the upper airways of SARS-CoV-2-negative (n = 18) and age-matched SARS-CoV-2-positive (n = 24) children and corresponding samples from adults (n = 44), covering an age range of 4 weeks to 77 years. Children displayed higher basal expression of relevant pattern recognition receptors such as MDA5 (IFIH1) and RIG-I (DDX58) in upper airway epithelial cells, macrophages and dendritic cells, resulting in stronger innate antiviral responses upon SARS-CoV-2 infection than in adults. We further detected distinct immune cell subpopulations including KLRC1 (NKG2A)[SUP]+[/SUP] cytotoxic T cells and a CD8[SUP]+[/SUP] T cell population with a memory phenotype occurring predominantly in children. Our study provides evidence that the airway immune cells of children are primed for virus sensing, resulting in a stronger early innate antiviral response to SARS-CoV-2 infection than in adults.
. 2021 Aug 18.
doi: 10.1038/s41587-021-01037-9. Online ahead of print.
Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children
J Loske[SUP] #[/SUP][SUP] 1 [/SUP], J Röhmel[SUP] #[/SUP][SUP] 2 [/SUP], S Lukassen[SUP] #[/SUP][SUP] 3 [/SUP], S Stricker[SUP] 2 [/SUP], V G Magalhães[SUP] 4 [/SUP], J Liebig[SUP] 3 [/SUP], R L Chua[SUP] 3 [/SUP], L Thürmann[SUP] 1 [/SUP], M Messingschlager[SUP] 1 [/SUP], A Seegebarth[SUP] 1 [/SUP], B Timmermann[SUP] 5 [/SUP], S Klages[SUP] 5 [/SUP], M Ralser[SUP] 6 [/SUP], B Sawitzki[SUP] 7 [/SUP], L E Sander[SUP] 8 9 [/SUP], V M Corman[SUP] 10 11 [/SUP], C Conrad[SUP] 3 [/SUP], S Laudi[SUP] 12 [/SUP], M Binder[SUP] 4 [/SUP], S Trump[SUP] 1 [/SUP], R Eils[SUP] 13 14 15 [/SUP], M A Mall[SUP] 2 9 [/SUP], I Lehmann[SUP] 1 9 16 [/SUP]
Affiliations
- PMID: 34408314
- DOI: 10.1038/s41587-021-01037-9
Abstract
Children have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and a substantially lower risk for developing severe coronavirus disease 2019 compared with adults. However, the molecular mechanisms underlying protection in younger age groups remain unknown. Here we characterize the single-cell transcriptional landscape in the upper airways of SARS-CoV-2-negative (n = 18) and age-matched SARS-CoV-2-positive (n = 24) children and corresponding samples from adults (n = 44), covering an age range of 4 weeks to 77 years. Children displayed higher basal expression of relevant pattern recognition receptors such as MDA5 (IFIH1) and RIG-I (DDX58) in upper airway epithelial cells, macrophages and dendritic cells, resulting in stronger innate antiviral responses upon SARS-CoV-2 infection than in adults. We further detected distinct immune cell subpopulations including KLRC1 (NKG2A)[SUP]+[/SUP] cytotoxic T cells and a CD8[SUP]+[/SUP] T cell population with a memory phenotype occurring predominantly in children. Our study provides evidence that the airway immune cells of children are primed for virus sensing, resulting in a stronger early innate antiviral response to SARS-CoV-2 infection than in adults.