Type Ⅲ Interferons are Critical Host Factors to Determine the Susceptibility to Influenza A Viral Infection in Allergic Nasal Mucosa

Abstract

Rationale: Interferon (IFN) is key component to control innate immunity in the respiratory epithelial cells and is responsible for the first defense phase of virus infection. A deficiency in IFN production from the respiratory epithelial cells is actually related with higher susceptibility to respiratory viral infections in asthma but less is known about allergic rhinitis (AR), the first portal of contact of respiratory infections. We studied whether allergic nasal mucosa would be more susceptible to influenza A virus (IAV) infection due to lower induction of IFN-related immune responses. Objectives: In this study, we aimed to determine whether IFN induction would be impaired in allergic nasal mucosa and to identify which IFN was correlated with higher viral loads in IAV-infected allergic nasal mucosa. Methods: IAV mRNA levels, viral titers and IFNs expression were compared in IAV-infected normal human nasal epithelial (NHNE, N=10) and allergic rhinitis nasal epithelial (ARNE, N=10) cells. And we used human nasal mucosa from healthy volunteers (N=72) and AR patients (N=29) were used to assess the induction of IFNs after IAV infection. Measurement and Main Results: IAV mRNA levels and viral titers were significantly higher in ARNE cells compared with NHNE cells. The mRNA levels of IFN-β and -λs were induced in NHNE and ARNE cells up to 3 days after IAV infection. Interestingly, induction of IFN-λ mRNA levels and the amount of secreted proteins were considerable lower in ARNE cells. Mean mRNA levels of IFN-λs were also significantly lower in human nasal mucosa of AR patients. We found that recombinant treatment of IFN-λ attenuated viral mRNA levels and viral titers in IAV-infected ARNE cells. Conclusion: Higher susceptibility of allergic nasal mucosa to IAV may depend on impairment of type Ⅲ IFN induction, and type Ⅲ IFN is a key mechanistic link between higher viral loads and control of IAV infection in allergic nasal mucosa.