Neutrophilic inflammation promotes SARS-CoV-2 infectivity and augments the inflammatory responses in airway epithelial cells

Ben A Calvert; Erik J. Quiroz; Zareeb Lorenzana; Ngan Doan; Seongjae Kim; Christiana N. Senger; Jeffrey J. Anders; Wiliam D. Wallace; Matthew P. Salomon; Jill Henley; Amy L. Ryan

doi:10.3389/fimmu.2023.1112870

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Neutrophilic inflammation promotes SARS-CoV-2 infectivity and augments the inflammatory responses in airway epithelial cells

Journal article

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Neutrophilic inflammation promotes SARS-CoV-2 infectivity and augments the inflammatory responses in airway epithelial cells

Ben A Calvert, Erik J. Quiroz, Zareeb Lorenzana, Ngan Doan, Seongjae Kim, Christiana N. Senger, Jeffrey J. Anders, Wiliam D. Wallace, Matthew P. Salomon, Jill Henley, …

Frontiers in immunology, Vol.14, 1112870

03/01/2023

DOI: 10.3389/fimmu.2023.1112870

PMCID: PMC10061003

PMID: 37006263

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https://doi.org/10.3389/fimmu.2023.1112870View

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Abstract

IntroductionIn response to viral infection, neutrophils release inflammatory mediators as part of the innate immune response, contributing to pathogen clearance through virus internalization and killing. Pre- existing co-morbidities correlating to incidence to severe COVID-19 are associated with chronic airway neutrophilia. Furthermore, examination of COVID-19 explanted lung tissue revealed a series of epithelial pathologies associated with the infiltration and activation of neutrophils, indicating neutrophil activity in response to SARS-CoV-2 infection.MethodsTo determine the impact of neutrophil-epithelial interactions on the infectivity and inflammatory responses to SARS-CoV-2 infection, we developed a co-culture model of airway neutrophilia. This model was infected with live SARS-CoV-2 virus the epithelial response to infection was evaluated.ResultsSARS-CoV-2 infection of airway epithelium alone does not result in a notable pro-inflammatory response from the epithelium. The addition of neutrophils induces the release of proinflammatory cytokines and stimulates a significantly augmented proinflammatory response subsequent SARS-CoV-2 infection. The resulting inflammatory responses are polarized with differential release from the apical and basolateral side of the epithelium. Additionally, the integrity of the \epithelial barrier is impaired with notable epithelial damage and infection of basal stem cells.ConclusionsThis study reveals a key role for neutrophil-epithelial interactions in determining inflammation and infectivity.

Cytokines

Inflammation

airway epithelium

cell-cell interactions

neutrophils

viral infection

Details

Title: Subtitle: Neutrophilic inflammation promotes SARS-CoV-2 infectivity and augments the inflammatory responses in airway epithelial cells
Creators: Ben A Calvert - Hastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, United States
Erik J. Quiroz - Hastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, United States
Zareeb Lorenzana - Hastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, United States
Ngan Doan - Hastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, United States
Seongjae Kim - The Salk Institute of Biological Studies, La Jolla, CA, United States
Christiana N. Senger - Hastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, United States
Jeffrey J. Anders - University of Iowa
Wiliam D. Wallace - Department of Pathology, University of Southern California, Los Angeles, CA, United States
Matthew P. Salomon - Department of Medicine, University of Southern California, Los Angeles, CA, United States
Jill Henley - Department of Medicine, University of Southern California, Los Angeles, CA, United States
Amy L. Ryan - Hastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, United States
Resource Type: Journal article
Publication Details: Frontiers in immunology, Vol.14, 1112870
DOI: 10.3389/fimmu.2023.1112870
PMID: 37006263
PMCID: PMC10061003
NLM abbreviation: Front Immunol
ISSN: 1664-3224
eISSN: 1664-3224
Publisher: Frontiers Media S.A
Grant note: DOI: 10.13039/100006501, name: Cystic Fibrosis Foundation Therapeutics, award: FIRTH17XX0, FIRTH21XX0
Language: English
Date published: 03/01/2023
Academic Unit: Anatomy and Cell Biology; Ophthalmology and Visual Sciences
Record Identifier: 9984380366002771

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