NON-TYPEABLE HAEMOPHILUS INFLUENZAE DOWNREGULATES RELEASE OF BETA-DEFENSIN-1 FROM BRONCHIAL EPITHELIAL CELLS
Tregidgo LJ., Cane JL., Bafadhel M.
Introduction: Beta defensin-1 is an antimicrobial peptide released from epithelial cells, acting to defend the host against microbial activity and colonisation. It is possible that reduction in release of this antimicrobial peptide contributes to the host inability to remove bacteria from the airway. We investigated the release of beta-defensin-1 from the bronchial epithelium, with and without Non-Typeable Haemophilus influenzae (NTHi) infection and studied the effects of corticosteroids on this. Method: Human bronchial epithelial cells from three healthy donors were grown to 90% confluence. Cells were treated with 16 nM, 1.6 nM and 0.16 nM Budesonide or 10 nM, 1 nM and 0.1 nM Fluticasone propionate as per clinical equivalence, for two hours prior to addition of 1 × 106 CFU of NTHi. Cells were incubated for a further two hours. Beta-defensin-1 was measured in supernatants by ELISA. Results: NTHi infection downregulated beta-defensin-1 release by 42% (mean basal release: 133.6 pg/ml, SD: 61.6, mean release with NTHi infection: 77.6 pg/ml, SD: 50.6. p = 0.0084). Addition of Budesonide or Fluticasone propionate to bronchial epithelial cells decreased beta-defensin-1 release from mean basal level to 106.2 pg/ml (SD: 79.4, p = 0.023) and 100.6 pg/ml (SD: 50.0, p = 0.083) respectively. This release is synergistically decreased upon NTHi infection with Budesonide and Fluticasone propionate treatment (mean with NTHi: 67.3 pg/ml, SD: 38.7. p = 0.039 and 64.4 pg/ml, SD: 26.1. p = 0.048) respectively compared to corticosteroid treatment only. No difference in beta-defensin-1 level was seen between low and high dose of either corticosteroid tested. Conclusion: NTHi inhibits beta-defensin-1 release from healthy bronchial epithelial cells. This release is dampened further by corticosteroid treatment and may be implicated in NTHi persistence in the airway in patients with chronic lung disease such as COPD.