TLR7 Promotes Chronic Airway Disease in RSV-infected Mice

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Oct 5

PMID 37795093

Authors

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 OLeary

Doug A Brooks

Stavros Selemidis

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

TLR7 Promotes Acute Inflammatory-Driven Lung Dysfunction in Influenza-Infected Mice but Prevents Late Airway Hyperresponsiveness.

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Toll-like receptor activation induces airway obstruction and hyperresponsiveness in guinea pigs.

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Liong S, Liong F, Mohsenipour M, Hill-Yardin E, Miles M, Selemidis S Cells. 2024; 13(20.

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