ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Organoids and Organ-On-A-Chip
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1587080
This article is part of the Research TopicRising Female Scientists in the Field of In Vitro Tissue ModelingView all 8 articles
Lung-Resident SARS-CoV-2 Peptide-Specific Immune Responses in Perfused 3D Human Lung Explant Models
Provisionally accepted- 1University of Alabama at Birmingham, Birmingham, United States
- 2Tulane University, New Orleans, Louisiana, United States
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Multi-specific and long-lasting T cell immunity has been recognized to indicate long term protection against pathogens including the novel coronavirus SARS-CoV-2, the causative agent of the COVID-19 pandemic. Functional significance of peripheral memory T cells in individuals recovering from COVID-19 (COVID-19 + ) are beginning to be appreciated; but the role of lung resident memory T cells (lung TRM) 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. Here, we utilize a perfused three-dimensional (3D) human lung tissue model and show preexisting local T cell immunity against SARS-CoV-2 proteins in lung tissues. We report ex vivo maintenance of functional multi-specific IFN-gamma secreting lung TRM 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 + . Further, lung tissue IgA levels were increased in COVID-19 + and responded to peptide stimulation. Our study highlights the importance of utilization of human lung tissue models to understand the local anti-viral immune response in the lung to protect against SARS-CoV-2 infection.
Keywords: Human lung tissue model, SARS-CoV-2 infection, COVID-19, Perfused lung explant, Local antiviral immune response
Received: 03 Mar 2025; Accepted: 30 May 2025.
Copyright: © 2025 Goliwas, Wood, Simmons, Khan, Khan, Wang, Ramachandran, Berry, Athar, Mobley, Kim, Thannickal, Harrod, Donahue and Deshane. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Kayla Goliwas, University of Alabama at Birmingham, Birmingham, United States
Jessy Deshane, University of Alabama at Birmingham, Birmingham, United States
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