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Nakayama, M. ; Marchi, H. ; Dmitrieva, A. ; Chakraborty, A. ; Merl-Pham, J. ; Hennen, E. ; Le Gleut, R. ; Ruppert, C.* ; Guenther, A.* ; Kahnert, K.* ; Behr, J.* ; Hilgendorff, A. ; Hauck, S.M. ; Adler, H. ; Staab-Weijnitz, C.A.

Quantitative proteomics of differentiated primary bronchial epithelial cells from chronic obstructive pulmonary disease and control identifies potential novel host factors post-influenza A virus infection.

Front. Microbiol. 13:957830 (2023)

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Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.

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BACKGROUND: Chronic obstructive pulmonary disease (COPD) collectively refers to chronic and progressive lung diseases that cause irreversible limitations in airflow. Patients with COPD are at high risk for severe respiratory symptoms upon influenza virus infection. Airway epithelial cells provide the first-line antiviral defense, but whether or not their susceptibility and response to influenza virus infection changes in COPD have not been elucidated. Therefore, this study aimed to compare the susceptibility of COPD- and control-derived airway epithelium to the influenza virus and assess protein changes during influenza virus infection by quantitative proteomics. MATERIALS AND METHODS: The presence of human- and avian-type influenza A virus receptor was assessed in control and COPD lung sections as well as in fully differentiated primary human bronchial epithelial cells (phBECs) by lectin- or antibody-based histochemical staining. PhBECs were from COPD lungs, including cells from moderate- and severe-stage diseases, and from age-, sex-, smoking, and history-matched control lung specimens. Protein profiles pre- and post-influenza virus infection in vitro were directly compared using quantitative proteomics, and selected findings were validated by qRT-PCR and immunoblotting. RESULTS: The human-type influenza receptor was more abundant in human airways than the avian-type influenza receptor, a property that was retained in vitro when differentiating phBECs at the air-liquid interface. Proteomics of phBECs pre- and post-influenza A virus infection with A/Puerto Rico/8/34 (PR8) revealed no significant differences between COPD and control phBECs in terms of flu receptor expression, cell type composition, virus replication, or protein profile pre- and post-infection. Independent of health state, a robust antiviral response to influenza virus infection was observed, as well as upregulation of several novel influenza virus-regulated proteins, including PLSCR1, HLA-F, CMTR1, DTX3L, and SHFL. CONCLUSION: COPD- and control-derived phBECs did not differ in cell type composition, susceptibility to influenza virus infection, and proteomes pre- and post-infection. Finally, we identified novel influenza A virus-regulated proteins in bronchial epithelial cells that might serve as potential targets to modulate the pathogenicity of infection and acute exacerbations.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Copd ; Flu Receptor ; Organotypic ; Primary Human Bronchial Epithelial Cells ; Proteomics; Air-liquid Interface; Expression; Cultures; Model; Receptors; Profile

ISSN (print) / ISBN 1664-302X

e-ISSN 1664-302X

Journal Frontiers in Microbiology

Quellenangaben Volume: 13, Article Number: 957830

Publisher Frontiers

Publishing Place Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Lung Health and Immunity (LHI)
Institute of Asthma and Allergy Prevention (IAP)
CF Statistical Consulting (CF-STATCON)
Research Unit Lung Repair and Regeneration (LRR)
CF Metabolomics & Proteomics (CF-MPC)

Grants Uehara Memorial Foundation
Shiga University of Medical Science
Helmholtz Association
German Research Foundation (DFG)
German Center for Lung Research (DZL)
German Federal Institute for Risk Assessment (BfR)