Corticosteroid Suppression of Antiviral Immunity Increases Bacterial Loads and Mucus Production in COPD Exacerbations

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Jun 10

PMID 29884817

Citations 99

Authors

Aran Singanayagam

Nicholas Glanville

Jason L Girkin

Yee Man Ching

Andrea Marcellini

James D Porter

Marie Toussaint

Ross P Walton

Lydia J Finney

Julia Aniscenko

Jie Zhu

Maria-Belen Trujillo-Torralbo

Maria Adelaide Calderazzo

Chris Grainge

Su-Ling Loo

Punnam Chander Veerati

Prabuddha S Pathinayake

Kristy S Nichol

Andrew T Reid

Phillip L James

Roberto Solari

Peter A B Wark

Darryl A Knight

Miriam F Moffatt

William O Cookson

Michael R Edwards

Patrick Mallia

Nathan W Bartlett

Sebastian L Johnston

Affiliations

Soon will be listed here.

Abstract

Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms. Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections. Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations. Exogenous interferon-β reverses these effects. FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways. Mice deficient in the type I interferon-α/β receptor (IFNAR1) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection. This study identifies type I interferon as a central regulator of antibacterial immunity and mucus production. Suppression of interferon by ICS during virus-induced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect.

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