TLR7 promotes chronic airway disease in RSV-infected mice.


Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2023
Historique:
received: 15 06 2023
accepted: 28 08 2023
medline: 6 10 2023
pubmed: 5 10 2023
entrez: 5 10 2023
Statut: epublish

Résumé

Respiratory syncytial virus (RSV) commonly infects the upper respiratory tract (URT) of humans, manifesting with mild cold or flu-like symptoms. However, in infants and the elderly, severe disease of the lower respiratory tract (LRT) often occurs and can develop into chronic airway disease. A better understanding of how an acute RSV infection transitions to a LRT chronic inflammatory disease is critically important to improve patient care and long-term health outcomes. To model acute and chronic phases of the disease, we infected wild-type C57BL/6 and toll-like receptor 7 knockout (TLR7 KO) mice with RSV and temporally assessed nasal, airway and lung inflammation for up to 42 days post-infection. We show that TLR7 reduced viral titers in the URT during acute infection but promoted pronounced pathogenic and chronic airway inflammation and hyperreactivity in the LRT. This study defines a hitherto unappreciated molecular mechanism of lower respiratory pathogenesis to RSV, highlighting the potential of TLR7 modulation to constrain RSV pathology to the URT.

Identifiants

pubmed: 37795093
doi: 10.3389/fimmu.2023.1240552
pmc: PMC10545951
doi:

Substances chimiques

Toll-Like Receptor 7 0
Tlr7 protein, mouse 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1240552

Informations de copyright

Copyright © 2023 Miles, Liong, Liong, Coward-Smith, Trollope, Oseghale, Erlich, Brooks, Logan, Hickey, Wang, Bozinovski, O’Leary, Brooks and Selemidis.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Mark A Miles (MA)

Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia.

Stella Liong (S)

Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia.

Felicia Liong (F)

Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia.

Madison Coward-Smith (M)

Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia.

Gemma S Trollope (GS)

Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia.

Osezua Oseghale (O)

Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia.

Jonathan R Erlich (JR)

Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia.

Robert D Brooks (RD)

Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia.

Jessica M Logan (JM)

Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia.

Shane Hickey (S)

Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia.

Hao Wang (H)

Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia.

Steven Bozinovski (S)

Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia.

John J O'Leary (JJ)

Discipline of Histopathology, School of Medicine, Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Dublin, Ireland.
Sir Patrick Dun's Laboratory, Central Pathology Laboratory, St James's Hospital, Dublin, Ireland.

Doug A Brooks (DA)

Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia.
Discipline of Histopathology, School of Medicine, Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Dublin, Ireland.

Stavros Selemidis (S)

Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia.

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Classifications MeSH