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Introduction. Impaired repair of airway epithelium may lead to persistence of inflammation and remodelling. Regeneration of injured epithelium is a complex phenomenon and the role of toll-like receptors (TLRs) and respiratory virus products in this process have not been established. Aim of the study. In this study we aimed to test if wound repair in nasal epithelial cells is modulated by microbial products and if this process was different in patients with allergic rhinitis and in healthy subjects. Materials and methods. Injured human nasal epithelial cells (hNECs) monolayers were incubated with the toll-like receptors agonists: poly (I:C) and lipopolisacharide (LPS); allergen Der p1, and supernatants from virus-infected epithelial cells. Regeneration of injured epithelium was assessed by measuring changes in the area of epithelial damage. Results. Addition of either poly (I:C) or LPS induced a dose depen-dant inhibition of wound repair in hNECs monolayers. Supernatants from RV1b-infected cells decreased epithelial cell regeneration after mechanical injury only in allergic patients. At baseline conditions the dynamics of epithelial repair was similar in allergic and non-allergic epithelium. However, inhibitory effects of innate stimuli on epithelial repair was stronger in patients with allergic rhinitis as compared to healthy individuals. Conclusions. This study showed that microbial products may affect regeneration of the nasal epithelium, and allergic patients are more susceptible to suppression of epithelial regeneration

The aim of this study was to assess the immune response to parainfluenza virus type 3 (PIV3), rhinovirus 1B (RV1B) and intracellular Toll-like receptors (TLR) agonists in nasal epithelial cells (NECs) from patients with allergic rhinitis and healthy controls. NECs were obtained from eight patients with allergic rhinitis (AR) and 11 non-atopic healthy controls (HC) by nasal scraping, grown to confluence and exposed to PIV3, RV1B infection or TLR-3 and TLR-7/8 agonists. Interferon (IFN)-λ1, IFN-α, IFN-β and regulated on activation, normal T expressed and secreted (RANTES) release into the cell culture supernatants was assessed at 8, 24 and 48 h upon infection or 8 and 24 h after stimulation with poly(I:C) and R848. mRNA levels of IFNs, RANTES, interferon regulatory transcription factor (IRF)3, IRF7 and viral gene copy number were determined using real-time polymerase chain reaction (RT-PCR). PIV3 but not RV1B replication 48 h after infection was significantly lower (P < 0·01) in NECs from AR patients compared to HC. PIV3 infection induced significantly less IFN-λ1 (both protein and mRNA) in NECs from AR compared to HC. IFN-β mRNA expression and RANTES protein release and mRNA expression tended to be smaller in AR compared HC cells in response to both viruses. Stimulation with TLR-3 agonist [poly (I:C)] induced similar IFN-λ1 and RANTES generation in AR and HC subjects. Viral infections in NECs induced IRF7 expression, which correlated with IFN and RANTES expression. These data suggest that virus proliferation rates and the immune response profile are different in nasal epithelial cells from patients with allergic rhinitis compared to healthy individuals. © 2016 British Society for Immunology

Summary The aim of this study was to assess the immune response to parainfluenza virus type 3 (PIV3), rhinovirus 1B (RV1B) and intracellular Toll-like receptors (TLR) agonists in nasal epithelial cells (NECs) from patients with allergic rhinitis and healthy controls. NECs were obtained from eight patients with allergic rhinitis (AR) and 11 non-atopic healthy controls (HC) by nasal scraping, grown to confluence and exposed to PIV3, RV1B infection or TLR-3 and TLR-7/8 agonists. Interferon (IFN)-λ1, IFN-α, IFN-β and regulated on activation, normal T expressed and secreted (RANTES) release into the cell culture supernatants was assessed at 8, 24 and 48 h upon infection or 8 and 24 h after stimulation with poly(I:C) and R848. mRNA levels of IFNs, RANTES, interferon regulatory transcription factor (IRF)3, IRF7 and viral gene copy number were determined using real-time polymerase chain reaction (RT-PCR). PIV3 but not RV1B replication 48 h after infection was significantly lower (P

Background: Current phenotyping of chronic rhinosinusitis (CRS) into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) might not adequately reflect the pathophysiologic diversity within patients with CRS. Objective: We sought to identify inflammatory endotypes of CRS. Therefore we aimed to cluster patients with CRS based solely on immune markers in a phenotype-free approach. Secondarily, we aimed to match clusters to phenotypes. Methods: In this multicenter case-control study patients with CRS and control subjects underwent surgery, and tissue was analyzed for IL-5, IFN-gamma, IL-17A, TNF-alpha, IL-22, IL-1 beta, IL-6, IL-8, eosinophilic cationic protein, myeloperoxidase, TGF-beta 1, IgE, Staphylococcus aureus enterotoxin-specific IgE, and albumin. We used partition-based clustering. Results: Clustering of 173 cases resulted in 10 clusters, of which 4 clusters with low or undetectable IL-5, eosinophilic cationic protein, IgE, and albumin concentrations, and 6 clusters with high concentrations of those markers. The group of IL-5-negative clusters, 3 clusters clinically resembled a predominant chronic rhinosinusitis without nasal polyps (CRSsNP) phenotype without increased asthma prevalence, and 1 cluster had a T(H)17 profile and had mixed CRSsNP/CRSwNP. The IL-5-positive clusters were divided into a group with moderate IL-5 concentrations, a mixed CRSsNP/CRSwNP and increased asthma phenotype, and a group with high IL-5 levels, an almost exclusive nasal polyp phenotype with strongly increased asthma prevalence. In the latter group, 2 clusters demonstrated the highest concentrations of IgE and asthma prevalence, with all samples expressing Staphylococcus aureus enterotoxin-specific IgE. Conclusion: Distinct CRS clusters with diverse inflammatory mechanisms largely correlated with phenotypes and further differentiated them and provided a more accurate description of the inflammatory mechanisms involved than phenotype information only.

Background The Global Allergy and Asthma European Network (GALEN) is a network of the leading European allergy clinical and research facilities and the GALEN Sinusitis Cohort is a database within this network. The aim of this cohort is to intensify research on rhinosinusitis phenoand endotypes, thus differentiating chronic rhinosinusitis (CRS) into smaller disease entities based on clinical, biological, and patient-reported outcomes.

Background Viral and bacterial infections can modulate the ongoing inflammation in both upper and lower airways of patients with chronic rhinosinusitis with nasal polyps (CRS/NP) and asthma. It was not clear if the protective immune response to pathogens may differ depending on the disease severity. Object: To compare serum IgG immune response against respiratory pathogens in patients with chronic airway disease (CRS/NP and asthma) with and without sensitivity to aspirin, and to refer the sensitization to severity of chronic rhinosinusitis. Methods We recruited 73 patients with CRS/NP and asthma with (43 patients) and without (30 patients) hypersensitivity to aspirin. The extent of mucosal hypertrophy in paranasal sinuses was assessed by CT scans and the sense of smell was valuated with “sniffing smell” test. Serum IgG immunoglobulin levels against respiratory pathogens: Respiratory Syncytial Virus (RSV), Adenowirus (ADV), Parainfluenza virus (PIV) and Mycoplasma pneumoniae were determined by ELISA. Results Patients with ASA-hypersensitivity had history of significantly more nasal polypectomies (P = 0.002), lower smell test score (P = 0.03) and higher mean paranasal CT score (P = 0.03) as compared to ASA-tolerant patients, reflecting higher severity of the upper airway disease. The percentage of positive serological testing to respiratory pathogens was very high in the whole group of patients with CRS/NP and asthma (RSV, 95.8%; ADV, 95.9%; PIV, 84.9% and Mycoplasma pneumonieae, 100% patients) without any difference between ASA-sensitive and ASA-tolerant subjects. Patients with ASA-sensitivity had significantly lower concentrations of PIV- specific IgG (mean 188.67 ± 34.46 U/mL versus 207.56 ± 30.036 U/mL; P < 0.04) as compared to ASA-tolerant subjects. There was a significant trend (P < 0.048) for lower PIV–specific IgG concentrations with increased number of polypectomies. No correlation of IgG immunoglobulin concentrations for other pathogens with the number of polypectomies, paranasal sinuses CT score or presences of smell were observed. Conclusions Patients with CRS/NP and asthma had high frequency of IgG immunoglobulin against common respiratory pathogens. Serum IgG immune response to paramyxoviruses may be related to the recurrence of nasal polyps and the presence of aspirin sensitivity.