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Type 2 inflammation reduces SARS-CoV-2 replication in the airway epithelium in allergic asthma through functional alteration of ciliated epithelial cells.
J Allergy Clin Immunol. 2023 Jul; 152(1):56-67.JA

Abstract

BACKGROUND

Despite well-known susceptibilities to other respiratory viral infections, individuals with allergic asthma have shown reduced susceptibility to severe coronavirus disease 2019 (COVID-19).

OBJECTIVE

We sought to identify mechanisms whereby type 2 inflammation in the airway protects against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by using bronchial airway epithelial cells (AECs) from aeroallergen-sensitized children with asthma and healthy nonsensitized children.

METHODS

We measured SARS-CoV-2 replication and ACE2 protein and performed bulk and single-cell RNA sequencing of ex vivo infected AEC samples with SARS-CoV-2 infection and with or without IL-13 treatment.

RESULTS

We observed that viral replication was lower in AECs from children with allergic asthma than those from in healthy nonsensitized children and that IL-13 treatment reduced viral replication only in children with allergic asthma and not in healthy children. Lower viral transcript levels were associated with a downregulation of functional pathways of the ciliated epithelium related to differentiation as well as cilia and axoneme production and function, rather than lower ACE2 expression or increases in goblet cells or mucus secretion pathways. Moreover, single-cell RNA sequencing identified specific subsets of relatively undifferentiated ciliated epithelium (which are common in allergic asthma and highly responsive to IL-13) that directly accounted for impaired viral replication.

CONCLUSION

Our results identify a novel mechanism of innate protection against SARS-CoV-2 in allergic asthma that provides important molecular and clinical insights during the ongoing COVID-19 pandemic.

Links

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Authors+Show Affiliations

Doni Jayavelu N
Systems Immunology Division, Benaroya Research Institute at Virginia Mason, Seattle, Wash.
Altman MC
Systems Immunology Division, Benaroya Research Institute at Virginia Mason, Seattle, Wash; Division of Allergy and Infectious Diseases, University of Washington School of Medicine, Seattle, Wash. Electronic address: maltman@benaroyaresearch.org.
Benson B
Division of Allergy and Infectious Diseases, University of Washington School of Medicine, Seattle, Wash.
Dufort MJ
Systems Immunology Division, Benaroya Research Institute at Virginia Mason, Seattle, Wash.
Vanderwall ER
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Wash.
Rich LM
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Wash.
White MP
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Wash.
Becker PM
National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, Md.
Togias A
National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, Md.
Jackson DJ
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
Debley JS
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Wash; Department of Pediatrics, Division of Pulmonary and Sleep Medicine, Seattle Children's Hospital, University of Washington, Seattle, Wash.

MeSH

ChildHumansSARS-CoV-2COVID-19Interleukin-13PandemicsAsthmaInflammationEpithelial CellsEpithelium

Pub Type(s)

Journal Article

Language

eng

PubMed ID

37001649

Citation

Doni Jayavelu, Naresh, et al. "Type 2 Inflammation Reduces SARS-CoV-2 Replication in the Airway Epithelium in Allergic Asthma Through Functional Alteration of Ciliated Epithelial Cells." The Journal of Allergy and Clinical Immunology, vol. 152, no. 1, 2023, pp. 56-67.
Doni Jayavelu N, Altman MC, Benson B, et al. Type 2 inflammation reduces SARS-CoV-2 replication in the airway epithelium in allergic asthma through functional alteration of ciliated epithelial cells. J Allergy Clin Immunol. 2023;152(1):56-67.
Doni Jayavelu, N., Altman, M. C., Benson, B., Dufort, M. J., Vanderwall, E. R., Rich, L. M., White, M. P., Becker, P. M., Togias, A., Jackson, D. J., & Debley, J. S. (2023). Type 2 inflammation reduces SARS-CoV-2 replication in the airway epithelium in allergic asthma through functional alteration of ciliated epithelial cells. The Journal of Allergy and Clinical Immunology, 152(1), 56-67. https://doi.org/10.1016/j.jaci.2023.03.021
Doni Jayavelu N, et al. Type 2 Inflammation Reduces SARS-CoV-2 Replication in the Airway Epithelium in Allergic Asthma Through Functional Alteration of Ciliated Epithelial Cells. J Allergy Clin Immunol. 2023;152(1):56-67. PubMed PMID: 37001649.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Type 2 inflammation reduces SARS-CoV-2 replication in the airway epithelium in allergic asthma through functional alteration of ciliated epithelial cells. AU - Doni Jayavelu,Naresh, AU - Altman,Matthew C, AU - Benson,Basilin, AU - Dufort,Matthew J, AU - Vanderwall,Elizabeth R, AU - Rich,Lucille M, AU - White,Maria P, AU - Becker,Patrice M, AU - Togias,Alkis, AU - Jackson,Daniel J, AU - Debley,Jason S, Y1 - 2023/03/29/ PY - 2022/09/30/received PY - 2023/03/05/revised PY - 2023/03/23/accepted PY - 2023/7/10/medline PY - 2023/4/1/pubmed PY - 2023/3/31/entrez KW - COVID-19 KW - IL-13 KW - SARS-CoV-2 KW - airway epithelial cells KW - asthma KW - children KW - epithelium SP - 56 EP - 67 JF - The Journal of allergy and clinical immunology JO - J Allergy Clin Immunol VL - 152 IS - 1 N2 - BACKGROUND: Despite well-known susceptibilities to other respiratory viral infections, individuals with allergic asthma have shown reduced susceptibility to severe coronavirus disease 2019 (COVID-19). OBJECTIVE: We sought to identify mechanisms whereby type 2 inflammation in the airway protects against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by using bronchial airway epithelial cells (AECs) from aeroallergen-sensitized children with asthma and healthy nonsensitized children. METHODS: We measured SARS-CoV-2 replication and ACE2 protein and performed bulk and single-cell RNA sequencing of ex vivo infected AEC samples with SARS-CoV-2 infection and with or without IL-13 treatment. RESULTS: We observed that viral replication was lower in AECs from children with allergic asthma than those from in healthy nonsensitized children and that IL-13 treatment reduced viral replication only in children with allergic asthma and not in healthy children. Lower viral transcript levels were associated with a downregulation of functional pathways of the ciliated epithelium related to differentiation as well as cilia and axoneme production and function, rather than lower ACE2 expression or increases in goblet cells or mucus secretion pathways. Moreover, single-cell RNA sequencing identified specific subsets of relatively undifferentiated ciliated epithelium (which are common in allergic asthma and highly responsive to IL-13) that directly accounted for impaired viral replication. CONCLUSION: Our results identify a novel mechanism of innate protection against SARS-CoV-2 in allergic asthma that provides important molecular and clinical insights during the ongoing COVID-19 pandemic. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/37001649/Type_2_inflammation_reduces_SARS_CoV_2_replication_in_the_airway_epithelium_in_allergic_asthma_through_functional_alteration_of_ciliated_epithelial_cells_ DB - PRIME DP - Unbound Medicine ER -