title: Th2 biased upper airway inflammation is associated with an impaired response to viral infection with Herpes simplex virus 1.
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.
authors.affiliation: Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Feng
authors.initials: F
authors.lastname: Lan
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Xiang Dong
authors.initials: XD
authors.lastname: Wang
authors.affiliation: Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Nauwynck
authors.affiliation: Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Holtappels
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Luo
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Airway Disease Infection Section, National Heart.
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
authors.affiliation: Allergy Department, 2nd Pediatric Clinic, University of Athens, Greece.
authors.forename: Nikolaos G
authors.initials: NG
authors.lastname: Papadopoulos
authors.affiliation: Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Claus
authors.initials: C
authors.lastname: Bachert
authors.affiliation: Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation; D007372:Interferons / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology*; D009298:Nasal Polyps / Q000276:immunology*; D012220:Rhinitis / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055815:Young Adult
chemical_list: D016207:Cytokines; C508609:IL10 protein, human; C508585:IL1B protein, human; C508599:IL5 protein, human; C508600:IL6 protein, human; D020381:Interleukin-17; D053583:Interleukin-1beta; D015848:Interleukin-5; D015850:Interleukin-6; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007073:Immunoglobulin E; D007372:Interferons