{"doi":"10.1002/alr.23164","title":"Epithelial innate immune response to <i>Pseudomonas aeruginosa–</i>derived flagellin in chronic rhinosinusitis","abstract":"BACKGROUND: Pseudomonas aeruginosa is a common colonizing pathogen in the upper respiratory tract and is associated with recalcitrant chronic rhinosinusitis (CRS). Herein we sought to characterize the effect of P. aeruginosa-derived flagellin on human sinonasal epithelial cell (HSNEC) immune responses and determine whether these pathways are disrupted in CRS. METHODS: Air-liquid interface cultures were established from CRS and healthy control donors. Cells were incubated with P. aeruginosa-derived flagellin for 24 hours and transcriptional changes were assessed using whole transcriptome RNA sequencing. Apical and basolateral secretion of the pro-inflammatory cytokines in interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 were measured after stimulation by lipopolysaccharide or flagellin and responses were compared between CRS and healthy control patients. RESULTS: HSNECs were weakly responsive to lipopolysaccharide, whereas flagellin stimulated a profound innate immune response dominated by TNF-α, IL-1β, and IL-17 signaling and activation of the IL-17C/IL-23 axis. CRS-derived HNSECs showed an altered innate immune response to flagellin, characterized by a profound increase in TNF-α secretion coupled with reduced IL-6 secretion. CONCLUSIONS: Flagellin activates a potent innate immune response in HSNECs characterized by pro-inflammatory mediators and cytokines/chemokines associated with neutrophilic inflammation. HSNECs from CRS patients have a dysregulated innate immune response to flagellin characterized by an imbalance between IL-6 and TNF-α secretion.","journal":"International Forum of Allergy & Rhinology","year":2023,"id":351036,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9489,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":86835,"name":"Quanhu Sheng","orcid":"0000-0001-8951-9295","position":1,"is_corresponding":false},{"id":361425,"name":"Li‐Ching Huang","orcid":"0000-0002-5959-7097","position":2,"is_corresponding":false},{"id":343814,"name":"Justin H. Turner","orcid":"0000-0002-5501-9900","position":3,"is_corresponding":false},{"id":304619,"name":"Ping Li","orcid":"0000-0002-7671-1584","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T01:12:37.409066Z","pmid":"37057820","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}