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Published on: September 22, 2023
Epithelial innate immune response to Pseudomonas aeruginosa-derived flagellin in chronic rhinosinusitis
Ping Li1, Quanhu Sheng2, Li-Ching Huang2
1Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
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.
Insights
Pseudomonas aeruginosa flagellin triggers a strong immune response in airway cells. In chronic rhinosinusitis (CRS), this response is dysregulated, showing increased TNF-α and decreased IL-6, contributing to inflammation.
Area of Science:
- Immunology
- Microbiology
- Otolaryngology
Background:
- Pseudomonas aeruginosa is a common pathogen in chronic rhinosinusitis (CRS).
- Flagellin, a component of P. aeruginosa, is a key immune stimulant.
- Understanding flagellin's role in CRS pathogenesis is crucial.
Purpose of the Study:
- To investigate the impact of P. aeruginosa flagellin on human sinonasal epithelial cell (HSNEC) immune responses.
- To determine if these immune pathways are altered in CRS patients.
Main Methods:
- Air-liquid interface cultures of HSNECs from CRS and healthy donors.
- Stimulation with P. aeruginosa flagellin and assessment of transcriptional changes via RNA sequencing.
- Measurement of pro-inflammatory cytokine secretion (IL-1β, TNF-α, IL-6).
Main Results:
- Flagellin induced a strong innate immune response in HSNECs, involving TNF-α, IL-1β, and IL-17 signaling.
- CRS-derived HSNECs exhibited an altered response to flagellin.
- CRS HSNECs showed increased TNF-α and decreased IL-6 secretion compared to controls.
Conclusions:
- Flagellin activates potent innate immune responses in HSNECs, promoting inflammation.
- HSNECs from CRS patients display a dysregulated immune response to flagellin.
- An imbalance in IL-6 and TNF-α secretion is characteristic of CRS HSNECs.
