Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children.

Autor: Loske J; Molecular Epidemiology Unit, Berlin Institute of Health at the Charité - Universitätsmedizin Berlin, Berlin, Germany., Röhmel J; Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu, Berlin, Germany., Lukassen S; Center for Digital Health, Berlin Institute of Health at the Charité - Universitätsmedizin Berlin, Berlin, Germany., Stricker S; Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu, Berlin, Germany., Magalhães VG; Research group 'Dynamics of Early Viral Infection and the Innate Antiviral Response', division F170, German Cancer Research Center (DKFZ), Heidelberg, Germany., Liebig J; Center for Digital Health, Berlin Institute of Health at the Charité - Universitätsmedizin Berlin, Berlin, Germany., Chua RL; Center for Digital Health, Berlin Institute of Health at the Charité - Universitätsmedizin Berlin, Berlin, Germany., Thürmann L; Molecular Epidemiology Unit, Berlin Institute of Health at the Charité - Universitätsmedizin Berlin, Berlin, Germany., Messingschlager M; Molecular Epidemiology Unit, Berlin Institute of Health at the Charité - Universitätsmedizin Berlin, Berlin, Germany., Seegebarth A; Molecular Epidemiology Unit, Berlin Institute of Health at the Charité - Universitätsmedizin Berlin, Berlin, Germany., Timmermann B; Max Planck Institute for Molecular Genetics, Berlin, Germany., Klages S; Max Planck Institute for Molecular Genetics, Berlin, Germany., Ralser M; Institute of Biochemistry, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Sawitzki B; Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany., Sander LE; Department of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.; German Center for Lung Research (DZL), associated partner, Berlin, Germany., Corman VM; Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.; German Centre for Infection Research (DZIF), Associated Partner Charité-Universitätsmedizin Berlin, Berlin, Germany., Conrad C; Center for Digital Health, Berlin Institute of Health at the Charité - Universitätsmedizin Berlin, Berlin, Germany., Laudi S; Department of Anesthesiology and Intensive Care, University Hospital Leipzig, Leipzig, Germany., Binder M; Research group 'Dynamics of Early Viral Infection and the Innate Antiviral Response', division F170, German Cancer Research Center (DKFZ), Heidelberg, Germany., Trump S; Molecular Epidemiology Unit, Berlin Institute of Health at the Charité - Universitätsmedizin Berlin, Berlin, Germany., Eils R; Center for Digital Health, Berlin Institute of Health at the Charité - Universitätsmedizin Berlin, Berlin, Germany. roland.eils@charite.de.; German Center for Lung Research (DZL), associated partner, Berlin, Germany. roland.eils@charite.de.; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. roland.eils@charite.de., Mall MA; Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu, Berlin, Germany.; German Center for Lung Research (DZL), associated partner, Berlin, Germany., Lehmann I; Molecular Epidemiology Unit, Berlin Institute of Health at the Charité - Universitätsmedizin Berlin, Berlin, Germany.; German Center for Lung Research (DZL), associated partner, Berlin, Germany.; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Jazyk: angličtina
Zdroj: Nature biotechnology [Nat Biotechnol] 2022 Mar; Vol. 40 (3), pp. 319-324. Date of Electronic Publication: 2021 Aug 18.
DOI: 10.1038/s41587-021-01037-9
Abstrakt: 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) + cytotoxic T cells and a CD8 + 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. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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