Frontiers in Immunology (Sep 2023)

TLR7 promotes chronic airway disease in RSV-infected mice

  • Mark A. Miles,
  • Stella Liong,
  • Felicia Liong,
  • Madison Coward-Smith,
  • Gemma S. Trollope,
  • Osezua Oseghale,
  • Jonathan R. Erlich,
  • Robert D. Brooks,
  • Jessica M. Logan,
  • Shane Hickey,
  • Hao Wang,
  • Steven Bozinovski,
  • John J. O’Leary,
  • John J. O’Leary,
  • Doug A. Brooks,
  • Doug A. Brooks,
  • Stavros Selemidis

DOI
https://doi.org/10.3389/fimmu.2023.1240552
Journal volume & issue
Vol. 14

Abstract

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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.

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