Inefficient antiviral response in reconstituted small-airway epithelium from chronic obstructive pulmonary disease patients following human parainfluenza virus type 3 infection.

Airway epithelium Pathogenesis Respiratory virus Transcriptome

Journal

Virology journal
ISSN: 1743-422X
Titre abrégé: Virol J
Pays: England
ID NLM: 101231645

Informations de publication

Date de publication:
02 Apr 2024
Historique:
received: 21 12 2023
accepted: 27 03 2024
medline: 3 4 2024
pubmed: 3 4 2024
entrez: 2 4 2024
Statut: epublish

Résumé

Chronic obstructive pulmonary disease (COPD) affects over 250 million individuals globally and stands as the third leading cause of mortality. Respiratory viral infections serve as the primary drivers of acute exacerbations, hastening the decline in lung function and worsening the prognosis. Notably, Human Parainfluenza Virus type 3 (HPIV-3) is responsible for COPD exacerbations with a frequency comparable to that of Respiratory Syncytial Virus and Influenza viruses. However, the impact of HPIV-3 on respiratory epithelium within the context of COPD remains uncharacterized.In this study, we employed in vitro reconstitution of lower airway epithelia from lung tissues sourced from healthy donors (n = 4) and COPD patients (n = 5), maintained under air-liquid interface conditions. Through a next-generation sequencing-based transcriptome analysis, we compared the cellular response to HPIV-3 infection.Prior to infection, COPD respiratory epithelia exhibited a pro-inflammatory profile, notably enriched in canonical pathways linked to antiviral response, B cell signaling, IL-17 signaling, and epithelial-mesenchymal transition, in contrast to non-COPD epithelia. Intriguingly, post HPIV-3 infection, only non-COPD epithelia exhibited significant enrichment in interferon signaling, pattern recognition receptors of viruses and bacteria, and other pathways involved in antiviral responses. This deficiency could potentially hinder immune cell recruitment essential for controlling viral infections, thus fostering prolonged viral presence and persistent inflammation.

Identifiants

pubmed: 38566231
doi: 10.1186/s12985-024-02353-7
pii: 10.1186/s12985-024-02353-7
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

78

Informations de copyright

© 2024. The Author(s).

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Auteurs

Louise Bondeelle (L)

Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.

Maud Salmona (M)

Virology Department, AP-HP, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, Paris, F-75010, France.

Véronique Houdouin (V)

Service de Pneumologie, APHP, Hôpital Robert-Debré, Paris, F-75010, France.

Elise Diaz (E)

Université Paris Cité, Inserm U976, INSIGHT Team, Paris, F-75010, France.

Jacques Dutrieux (J)

Université Paris Cité, Institut Cochin, INSERM, U1016, CNRS, UMR8104, Paris, F-75014, France.

Séverine Mercier-Delarue (S)

Virology Department, AP-HP, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, Paris, F-75010, France.

Samuel Constant (S)

Epithelix Sarl, Geneva, 1228, Switzerland.

Song Huang (S)

Epithelix Sarl, Geneva, 1228, Switzerland.

Anne Bergeron (A)

Pneumology Department, Geneva University Hospitals, Geneva, Switzerland.

Jérôme LeGoff (J)

Virology Department, AP-HP, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, Paris, F-75010, France. jerome.le-goff@aphp.fr.
Université Paris Cité, Inserm U976, INSIGHT Team, Paris, F-75010, France. jerome.le-goff@aphp.fr.

Classifications MeSH