TLR7 promotes chronic airway disease in RSV-infected mice

Frontiers in Immunology

Immunology

Mark A. Miles¹  Steven Bozinovski¹  Stella Liong¹  Hao Wang¹  Madison Coward-Smith¹  Osezua Oseghale¹  Gemma S. Trollope¹  Felicia Liong¹  Stavros Selemidis¹  Jonathan R. Erlich¹  Robert D. Brooks²  Jessica M. Logan²  Shane Hickey²  Doug A. Brooks³  John J. O’Leary⁴ 

[1] Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia;Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia;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;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;

关键词: toll-like receptor 7;    respiratory syncytial virus;    inflammation;    airway hyperreactivity;    viral infection;   

DOI  :  10.3389/fimmu.2023.1240552

 received in 2023-06-15, accepted in 2023-08-28,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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