Th2 biased upper airway inflammation is associated with an impaired response to viral infection with Herpes simplex virus 1

Background: We aimed to elucidate possible differences in antiviral defense in chronic rhinosinusitis with nasal polyps (CRSwNP) mucosal tissue compared to healthy mucosal tissue (HMT) upon herpes simplex virus 1 (HSV1) exposure. Methodology: HMT and CRSwNP samples were infected with HSV1. We visualized the virus location by immunofluorescence and monitored invasion by a score. The mediators Interferon (IFN)-alpha, IFN-beta, IFN-lambda, IFN-gamma, Interleukin (IL)-6, IL-1 beta, Tumor necrosis factor (TNF)-alpha, IL-17, IL-5, IL-10 were measured in culture supernatants at baseline and at 24h, 48h and 72h after virus incubation. Results: CRSwNP mucosal tissue showed a significant deficit in IFN-gamma and IL-17 release within 24 to 72 hours after infection in comparison to HMT, at the same time releasing significantly more pro-inflammatory cytokines including IL-1 beta and TNF-alpha. These findings were associated with significantly higher viral invasion scores at 48 and 72 h in CRSwNP mucosa compared to those for the HMT. Conclusions: We demonstrate for the first time in a human ex-vivo mucosal model that the inadequate response of CRSwNP may be associated with a deeper intrusion of viruses into the mucosal tissue, and may contribute to more and longer symptoms upon acute infection, but also to the persistence of inflammation in CRSwNP tissue