Previous Influenza Infection Exacerbates Allergen Specific Response and Impairs Airway Barrier Integrity in Pre-Sensitized Mice.

Kevin Looi,Graeme R Zosky,Kara L Perks,Darryl A Knight,Alexander N Larcombe,Luke J Berry,Stephen M Stick,Anthony Kicic,Paul Rigby

doi:10.3390/ijms22168790

Abstract

In this study we assessed the effects of antigen exposure in mice pre-sensitized with allergen following viral infection on changes in lung function, cellular responses and tight junction expression. Female BALB/c mice were sensitized to ovalbumin and infected with influenza A before receiving a second ovalbumin sensitization and challenge with saline, ovalbumin (OVA) or house dust mite (HDM). Fifteen days post-infection, bronchoalveolar inflammation, serum antibodies, responsiveness to methacholine and barrier integrity were assessed. There was no effect of infection alone on bronchoalveolar lavage cellular inflammation 15 days post-infection; however, OVA or HDM challenge resulted in increased bronchoalveolar inflammation dominated by eosinophils/neutrophils or neutrophils, respectively. Previously infected mice had higher serum OVA-specific IgE compared with uninfected mice. Mice previously infected, sensitized and challenged with OVA were most responsive to methacholine with respect to airway resistance, while HDM challenge caused significant increases in both tissue damping and tissue elastance regardless of previous infection status. Previous influenza infection was associated with decreased claudin-1 expression in all groups and decreased occludin expression in OVA or HDM-challenged mice. This study demonstrates the importance of the respiratory epithelium in pre-sensitized individuals, where influenza-infection-induced barrier disruption resulted in increased systemic OVA sensitization and downstream effects on lung function.

Highlights

IntroductionComplex disease of the airways affecting both children and adults
Asthma is a multifactorial, complex disease of the airways affecting both children and adults
We investigated the effects of influenza infection on mice, pre-sensitized with OVA

Summary

Introduction

Complex disease of the airways affecting both children and adults. The role of the airway epithelium in the pathogenesis of asthma has been extensively studied, with factors such as its immune functions [2] and its inherent abnormalities in asthmatic patients [3] being key foci This is understandable, as the airway epithelial layer is the frontline of defense against aeropathogens through the establishment and maintenance of a physical barrier [4,5,6]. Of importance are the tight junctions (TJ), which are typically located at the apical borders of adjacent epithelial cells where they serve to regulate the movement of ions and solutes as well as to prevent unwanted migration of pathogens and their products to the subepithelial space [8] They play a vital role in the maintenance of a healthy and intact airway epithelium [9]. Damage to the epithelial barrier, including disruption in the TJ proteins via environmental pollutants, aeroallergens or respiratory pathogens, has been shown to increase the paracellular traffic of pathogenic molecules into the lung interstitium [5]

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