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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Severe lower respiratory tract disease following influenza A virus (IAV) infection is characterized by excessive inflammation and lung tissue damage, and this can impair lung function. The effect of toll-like receptor 7 (TLR7), which detects viral RNA to initiate antiviral and proinflammatory responses to IAV, on lung function during peak infection and in the resolution phase is not fully understood. Using wild-type (WT) C57BL/6 and TLR7 knockout (TLR7 KO) mice, we found that IAV infection induced airway dysfunction in both genotypes, although in TLR7 KO mice, this dysfunction manifested later, did not affect lung tissue elastance and damping, and was associated with a different immune phenotype. A positive correlation was found between lung dysfunction and the infiltration of neutrophils and Ly6Clo patrolling monocytes at day 7 post-infection. Conversely, in TLR7 KO mice, eosinophil and CD8+ cytotoxic T cells were associated with airway hyperactivity at day 14. IL-5 expression was higher in the airways of IAV-infected TLR7 KO mice, suggesting an enhanced Th2 response due to TLR7 deficiency. This study highlights an underappreciated duality of TLR7 in IAV disease: promoting inflammation-driven lung dysfunction during the acute infection but suppressing eosinophilic and CD8+ T cell-dependent hyperresponsiveness during disease resolution.

Details

Title
TLR7 Promotes Acute Inflammatory-Driven Lung Dysfunction in Influenza-Infected Mice but Prevents Late Airway Hyperresponsiveness
Author
Miles, Mark A 1   VIAFID ORCID Logo  ; Liong, Stella 1   VIAFID ORCID Logo  ; Liong, Felicia 1 ; Trollope, Gemma S 1 ; Wang, Hao 1   VIAFID ORCID Logo  ; Brooks, Robert D 2 ; Bozinovski, Steven 1 ; John J O’Leary 3   VIAFID ORCID Logo  ; Brooks, Doug A 2   VIAFID ORCID Logo  ; Selemidis, Stavros 1   VIAFID ORCID Logo 

 Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia; [email protected] (M.A.M.); [email protected] (S.L.); [email protected] (F.L.); [email protected] (G.S.T.); [email protected] (H.W.); [email protected] (S.B.) 
 Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia; [email protected] (R.D.B.); [email protected] (D.A.B.) 
 Discipline of Histopathology, School of Medicine, Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, D08 XW7X Dublin, Ireland; Sir Patrick Dun’s Laboratory, Central Pathology Laboratory, St James’s Hospital, D08 XW7X Dublin, Ireland 
First page
13699
Publication year
2024
Publication date
2024
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3149648627
Copyright
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.