Neutrophilic inflammation promotes SARS-CoV-2 infectivity and augments the inflammatory responses in airway epithelial cells
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 chr...
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| Format: | Article |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1112870/full |
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| author | Ben A. Calvert Ben A. Calvert Erik J. Quiroz Erik J. Quiroz 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 Amy L. Ryan Amy L. Ryan |
| author_facet | Ben A. Calvert Ben A. Calvert Erik J. Quiroz Erik J. Quiroz 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 Amy L. Ryan Amy L. Ryan |
| author_sort | Ben A. Calvert |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T00:14:52Z |
| format | Article |
| id | doaj.art-dc8fb565c2d0492690688a8a73f81fbe |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T00:14:52Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-dc8fb565c2d0492690688a8a73f81fbe2023-03-16T06:32:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-03-011410.3389/fimmu.2023.11128701112870Neutrophilic inflammation promotes SARS-CoV-2 infectivity and augments the inflammatory responses in airway epithelial cellsBen A. Calvert0Ben A. Calvert1Erik J. Quiroz2Erik J. Quiroz3Erik J. Quiroz4Zareeb Lorenzana5Ngan Doan6Seongjae Kim7Christiana N. Senger8Jeffrey J. Anders9Wiliam D. Wallace10Matthew P. Salomon11Jill Henley12Amy L. Ryan13Amy L. Ryan14Amy L. Ryan15Hastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa, IA, United StatesHastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa, IA, United StatesDepartment of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, United StatesHastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, United StatesHastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, United StatesThe Salk Institute of Biological Studies, La Jolla, CA, United StatesHastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa, IA, United StatesDepartment of Pathology, University of Southern California, Los Angeles, CA, United StatesDepartment of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Medicine, University of Southern California, Los Angeles, CA, United StatesHastings Center for Pulmonary Research, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa, IA, United StatesDepartment of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, United StatesIntroductionIn 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1112870/fullairway epitheliumcell-cell interactionscytokinesinflammationneutrophilsviral infection |
| spellingShingle | Ben A. Calvert Ben A. Calvert Erik J. Quiroz Erik J. Quiroz 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 Amy L. Ryan Amy L. Ryan Neutrophilic inflammation promotes SARS-CoV-2 infectivity and augments the inflammatory responses in airway epithelial cells Frontiers in Immunology airway epithelium cell-cell interactions cytokines inflammation neutrophils viral infection |
| title | Neutrophilic inflammation promotes SARS-CoV-2 infectivity and augments the inflammatory responses in airway epithelial cells |
| title_full | Neutrophilic inflammation promotes SARS-CoV-2 infectivity and augments the inflammatory responses in airway epithelial cells |
| title_fullStr | Neutrophilic inflammation promotes SARS-CoV-2 infectivity and augments the inflammatory responses in airway epithelial cells |
| title_full_unstemmed | Neutrophilic inflammation promotes SARS-CoV-2 infectivity and augments the inflammatory responses in airway epithelial cells |
| title_short | Neutrophilic inflammation promotes SARS-CoV-2 infectivity and augments the inflammatory responses in airway epithelial cells |
| title_sort | neutrophilic inflammation promotes sars cov 2 infectivity and augments the inflammatory responses in airway epithelial cells |
| topic | airway epithelium cell-cell interactions cytokines inflammation neutrophils viral infection |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1112870/full |
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