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

Abstract

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. 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)-α, IFN-β, IFN-λ, IFN-γ, Interleukin (IL)-6, IL-1β, Tumor necrosis factor (TNF)-α, IL-17, IL-5, IL-10 were measured in culture supernatants at baseline and at 24 h, 48 h and 72 h after virus incubation. CRSwNP mucosal tissue showed a significant deficit in IFN-γ 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-1β and TNF-α. These findings were associated with significantly higher viral invasion scores at 48 and 72 h in CRSwNP mucosa compared to those for the HMT. 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.