Lung-resident SARS-CoV-2 peptide-specific immune responses in perfused 3D human lung explant models
IntroductionMulti-specific and long-lasting T-cell immunity has been recognized to indicate long-term protection against pathogens, including the novel coronavirus, SARS-CoV-2, which is the causative agent of the COVID-19 pandemic. Functional significance of peripheral memory T cells in individuals...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2025.1587080/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1839636239440936960 |
|---|---|
| author | Kayla F. Goliwas Anthony M. Wood Christopher S. Simmons Rabisa Khan Saad A. Khan Yong Wang Rekha Ramachandran Joel L. Berry Mohammad Athar James A. Mobley Young-il Kim Victor J. Thannickal Kevin S. Harrod James M. Donahue Jessy S. Deshane |
| author_facet | Kayla F. Goliwas Anthony M. Wood Christopher S. Simmons Rabisa Khan Saad A. Khan Yong Wang Rekha Ramachandran Joel L. Berry Mohammad Athar James A. Mobley Young-il Kim Victor J. Thannickal Kevin S. Harrod James M. Donahue Jessy S. Deshane |
| author_sort | Kayla F. Goliwas |
| collection | DOAJ |
| description | IntroductionMulti-specific and long-lasting T-cell immunity has been recognized to indicate long-term protection against pathogens, including the novel coronavirus, SARS-CoV-2, which is the causative agent of the COVID-19 pandemic. Functional significance of peripheral memory T cells in individuals recovered from COVID-19 (COVID-19+) is beginning to be appreciated; however, the role of lung tissue-resident memory (lung TRM) T cells in SARS-CoV-2 infection is still being investigated. This is, in part, due to the lack of preclinical tissue models available to follow the convalescence period.MethodsHere, we utilize a perfused three-dimensional (3D) human lung-tissue model and show pre-existing local T-cell immunity against SARS-CoV-2 proteins in lung tissues.ResultsWe report ex vivo maintenance of functional multi-specific IFN-γ-secreting lung TRM T cells in COVID-19+ and their induction in lung tissues of vaccinated COVID-19+ subjects. Importantly, we identify SARS-CoV-2 peptide-responding memory B cells and IgA+ plasma cells in ex vivo cultured lung tissues of COVID-19+. Furthermore, lung tissue IgA levels were increased in COVID-19+ and responded to peptide stimulation.DiscussionIn our study, we highlight the importance of utilization of human lung-tissue models to understand the local antiviral immune response in the lung to protect against SARS-CoV-2 infection. |
| format | Article |
| id | doaj-art-d29aa2f1636e4739b10c8c9e8e05109c |
| institution | Matheson Library |
| issn | 2296-4185 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj-art-d29aa2f1636e4739b10c8c9e8e05109c2025-07-08T05:26:40ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852025-07-011310.3389/fbioe.2025.15870801587080Lung-resident SARS-CoV-2 peptide-specific immune responses in perfused 3D human lung explant modelsKayla F. Goliwas0Anthony M. Wood1Christopher S. Simmons2Rabisa Khan3Saad A. Khan4Yong Wang5Rekha Ramachandran6Joel L. Berry7Mohammad Athar8James A. Mobley9Young-il Kim10Victor J. Thannickal11Kevin S. Harrod12James M. Donahue13Jessy S. Deshane14Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Medicine, Division of Preventative Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Dermatology, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Medicine, Division of Preventative Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesJohn W. Deming Department of Medicine, Tulane University School of Medicine and Southeast Veterans Healthcare System, New Orleans, LA, United StatesDepartment of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Surgery, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United StatesIntroductionMulti-specific and long-lasting T-cell immunity has been recognized to indicate long-term protection against pathogens, including the novel coronavirus, SARS-CoV-2, which is the causative agent of the COVID-19 pandemic. Functional significance of peripheral memory T cells in individuals recovered from COVID-19 (COVID-19+) is beginning to be appreciated; however, the role of lung tissue-resident memory (lung TRM) T cells in SARS-CoV-2 infection is still being investigated. This is, in part, due to the lack of preclinical tissue models available to follow the convalescence period.MethodsHere, we utilize a perfused three-dimensional (3D) human lung-tissue model and show pre-existing local T-cell immunity against SARS-CoV-2 proteins in lung tissues.ResultsWe report ex vivo maintenance of functional multi-specific IFN-γ-secreting lung TRM T cells in COVID-19+ and their induction in lung tissues of vaccinated COVID-19+ subjects. Importantly, we identify SARS-CoV-2 peptide-responding memory B cells and IgA+ plasma cells in ex vivo cultured lung tissues of COVID-19+. Furthermore, lung tissue IgA levels were increased in COVID-19+ and responded to peptide stimulation.DiscussionIn our study, we highlight the importance of utilization of human lung-tissue models to understand the local antiviral immune response in the lung to protect against SARS-CoV-2 infection.https://www.frontiersin.org/articles/10.3389/fbioe.2025.1587080/fullhuman lung-tissue modelSARS-CoV-2 infectionCOVID-19perfused lung explantlocal antiviral immune response |
| spellingShingle | Kayla F. Goliwas Anthony M. Wood Christopher S. Simmons Rabisa Khan Saad A. Khan Yong Wang Rekha Ramachandran Joel L. Berry Mohammad Athar James A. Mobley Young-il Kim Victor J. Thannickal Kevin S. Harrod James M. Donahue Jessy S. Deshane Lung-resident SARS-CoV-2 peptide-specific immune responses in perfused 3D human lung explant models Frontiers in Bioengineering and Biotechnology human lung-tissue model SARS-CoV-2 infection COVID-19 perfused lung explant local antiviral immune response |
| title | Lung-resident SARS-CoV-2 peptide-specific immune responses in perfused 3D human lung explant models |
| title_full | Lung-resident SARS-CoV-2 peptide-specific immune responses in perfused 3D human lung explant models |
| title_fullStr | Lung-resident SARS-CoV-2 peptide-specific immune responses in perfused 3D human lung explant models |
| title_full_unstemmed | Lung-resident SARS-CoV-2 peptide-specific immune responses in perfused 3D human lung explant models |
| title_short | Lung-resident SARS-CoV-2 peptide-specific immune responses in perfused 3D human lung explant models |
| title_sort | lung resident sars cov 2 peptide specific immune responses in perfused 3d human lung explant models |
| topic | human lung-tissue model SARS-CoV-2 infection COVID-19 perfused lung explant local antiviral immune response |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2025.1587080/full |
| work_keys_str_mv | AT kaylafgoliwas lungresidentsarscov2peptidespecificimmuneresponsesinperfused3dhumanlungexplantmodels AT anthonymwood lungresidentsarscov2peptidespecificimmuneresponsesinperfused3dhumanlungexplantmodels AT christopherssimmons lungresidentsarscov2peptidespecificimmuneresponsesinperfused3dhumanlungexplantmodels AT rabisakhan lungresidentsarscov2peptidespecificimmuneresponsesinperfused3dhumanlungexplantmodels AT saadakhan lungresidentsarscov2peptidespecificimmuneresponsesinperfused3dhumanlungexplantmodels AT yongwang lungresidentsarscov2peptidespecificimmuneresponsesinperfused3dhumanlungexplantmodels AT rekharamachandran lungresidentsarscov2peptidespecificimmuneresponsesinperfused3dhumanlungexplantmodels AT joellberry lungresidentsarscov2peptidespecificimmuneresponsesinperfused3dhumanlungexplantmodels AT mohammadathar lungresidentsarscov2peptidespecificimmuneresponsesinperfused3dhumanlungexplantmodels AT jamesamobley lungresidentsarscov2peptidespecificimmuneresponsesinperfused3dhumanlungexplantmodels AT youngilkim lungresidentsarscov2peptidespecificimmuneresponsesinperfused3dhumanlungexplantmodels AT victorjthannickal lungresidentsarscov2peptidespecificimmuneresponsesinperfused3dhumanlungexplantmodels AT kevinsharrod lungresidentsarscov2peptidespecificimmuneresponsesinperfused3dhumanlungexplantmodels AT jamesmdonahue lungresidentsarscov2peptidespecificimmuneresponsesinperfused3dhumanlungexplantmodels AT jessysdeshane lungresidentsarscov2peptidespecificimmuneresponsesinperfused3dhumanlungexplantmodels |