Viral and host factors determine innate immune responses in airway epithelial cells from children with wheeze and atopy.

ABSTRACT

BACKGROUND: Airway epithelial cells (AEC) from patients with asthma, appear to have an impaired interferon (IFN)-ß and -λ response to infection with rhinovirus. OBJECTIVES: To determine if impaired IFN responses can be identified in young children at risk of developing asthma due to atopy and/or early life wheeze, and if the site of infection or the infecting virus influence the antiviral response. METHODS: Nasal (N) and tracheal (T) epithelial cells (EC) were collected from children categorised with atopy and/or wheeze based on specific IgE to locally common aeroallergens and a questionnaire concerning respiratory health. Submerged primary cultures were infected with respiratory syncytial virus (RSV) or human metapneumovirus (hMPV), and IFN production, inflammatory cytokine expression and viral replication quantified. RESULTS: Nasal epithelial cells (NEC), but not tracheal epithelial cells (TEC), from children with wheeze and/or atopy produced less IFN-ß, but not IFN-λ, in response to RSV infection; this was associated with higher viral shedding. However, IFN-regulated factors IRF-7, Mx-1 and CXCL-10, and inflammatory cytokines were not differentially regulated. NECs and TECs from children with wheeze and/or atopy demonstrated no impairment of the IFN response (ß or λ) to hMPV infection. Despite this, more hMPV was shed from these cells. CONCLUSIONS: AECs from children with wheeze and/or atopy do not have an intrinsic defect in the production of IFN-ß or -λ, however, this response is influenced by the infecting virus. Higher viral load is associated with atopy and wheeze suggesting an impaired antiviral response to RSV and hMPV that is not influenced by production of IFNs.