Intranasal and epicutaneous administration of Toll-like receptor 7 (TLR7) agonists provides protection against influenza A virus-induced morbidity in mice

To, E, Erlich, J, Liong, F, Luong, R, Liong, S, Bozinovski, S, Seow, H, O'Leary, J, Brooks, D, Vlahos, R and Selemidis, S 2019, 'Intranasal and epicutaneous administration of Toll-like receptor 7 (TLR7) agonists provides protection against influenza A virus-induced morbidity in mice', Scientific Reports, vol. 9, no. 1, pp. 1-15.


Document type: Journal Article
Collection: Journal Articles

Title Intranasal and epicutaneous administration of Toll-like receptor 7 (TLR7) agonists provides protection against influenza A virus-induced morbidity in mice
Author(s) To, E
Erlich, J
Liong, F
Luong, R
Liong, S
Bozinovski, S
Seow, H
O'Leary, J
Brooks, D
Vlahos, R
Selemidis, S
Year 2019
Journal name Scientific Reports
Volume number 9
Issue number 1
Start page 1
End page 15
Total pages 15
Publisher Nature Publishing Group
Abstract Toll-like receptor 7 (TLR7) is a pattern recognition receptor that recognizes viral RNA following endocytosis of the virus and initiates a powerful immune response characterized by Type I IFN production and pro-inflammatory cytokine production. Despite this immune response, the virus causes very significant pathology, which may be inflammation-dependent. In the present study, we examined the effect of intranasal delivery of the TLR7 agonist, imiquimod or its topical formulation Aldara, on the inflammation and pathogenesis caused by IAV infection. In mice, daily intranasal delivery of imiquimod prevented peak viral replication, bodyweight loss, airway and pulmonary inflammation, and lung neutrophils. Imiquimod treatment also resulted in a significant reduction in pro-inflammatory neutrophil chemotactic cytokines and prevented the increase in viral-induced lung dysfunction. Various antibody isotypes (IgG1, IgG2a, total IgG, IgE and IgM), which were increased in the BALF following influenza A virus infection, were further increased with imiquimod. While epicutaneous application of Aldara had a significant effect on body weight, it did not reduce neutrophil and eosinophil airway infiltration; indicating less effective drug delivery for this formulation. We concluded that intranasal imiquimod facilitates a more effective immune response, which can limit the pathology associated with influenza A virus infection.
Subject Basic Pharmacology
Respiratory Diseases
DOI - identifier 10.1038/s41598-019-38864-5
Copyright notice © 2019, The Author(s)
ISSN 2045-2322
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