Type III III interferons are critical host factors that determine susceptibility to Influenza A viral infection in allergic nasal mucosa

摘要

Summary Background Allergic respiratory conditions have been associated with increased susceptibility to viral infection due to impaired interferon ( IFN )‐related immune responses, but the mechanisms for reinforcement of mucosal immunity against viral infection in allergic diseases are largely unknown. Objectives To determine whether IFN induction would be impaired in allergic nasal mucosa and to identify whether higher loads of influenza A virus ( IAV ) in allergic nasal mucosa could be controlled with IFN treatment. Methods Influenza A virus mRNA , viral titres and IFN expression were compared in IAV ‐infected normal human nasal epithelial ( NHNE , N?=?10) and allergic rhinitis nasal epithelial ( ARNE , N?=?10) cells. We used in?vivo model of allergic rhinitis ( BALB /c mice, N?=?10) and human nasal mucosa from healthy volunteers (N?=?72) and allergic rhinitis patients (N?=?29) to assess the induction of IFN s after IAV infection. Results Influenza A virus mRNA levels and viral titres were significantly higher in ARNE compared with NHNE cells. IFN ‐β and IFN‐λs were induced in NHNE and ARNE cells up to 3?days after IAV infection. Interestingly, induction of IFN ‐λs mRNA levels and the amount of secreted proteins were considerably lower in ARNE cells. The mean IFN ‐λs mRNA level was also significantly lower in the nasal mucosa of AR patients, and we found that recombinant IFN ‐λ treatment attenuated viral mRNA levels and viral titres in IAV ‐infected ARNE cells. In vivo AR mouse exhibited higher viral load after IAV infection, but intranasal inoculation of IFN ‐λ completely decreased IAV protein expression and viral titre in nasal mucosa of IAV ‐infected AR mouse. Conclusion Higher susceptibility of the 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.