Pre-activated anti-viral innate immunity in the upper airways controls early SARS-CoV-2 infection in children
| Autor: | Leif E. Sander, Vladimir Gonçalves Magalhães, Sebastian Stricker, Saskia Trump, Irina Lehmann, Sven Laudi, Sven Klages, Johannes Liebig, Victor M. Corman, Jennifer Loske, Roland Eils, Soeren Lukassen, Bernd Timmermann, Marcus A. Mall, Christian Conrad, Markus Ralser, Anke Seegebarth, Marey Messingschlager, Birgit Sawitzki, Marco Binder, Jobst Röhmel, Loreen Thürmann, Robert Lorenz Chua |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Interferon-Induced Helicase IFIH1 viruses CD8-Positive T-Lymphocytes Applied Microbiology and Biotechnology Basal (phylogenetics) Cytotoxic T cell Receptors Immunologic Child education.field_of_study Pattern recognition receptor Middle Aged medicine.anatomical_structure Child Preschool DEAD Box Protein 58 Molecular Medicine Female Single-Cell Analysis Biotechnology Adult Adolescent T cell Population Biomedical Engineering Bronchi Bioengineering Biology Virus Young Adult Immune system Immunity medicine Humans education Aged Innate immune system SARS-CoV-2 business.industry Macrophages Infant Newborn COVID-19 Infant Epithelial Cells Dendritic Cells Immunity Innate Immunology business Airway CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | Nature Biotechnology |
| Popis: | 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. Single-cell sequencing reveals pre-activated immunity as important for milder COVID-19 symptoms in children. |
| Databáze: | OpenAIRE |
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