Primary ciliary dyskinesia ciliated airway cells show increased susceptibility to Haemophilus influenzae biofilm formation

Authors

Woolf Walker, University of Southampton, University Hospital Southampton
Claire Jackson, University of Southampton, University Hospital Southampton
Raymond Allan, University of Southampton, Wellcome Trust Clinical Research Facility
Samuel Collins, University Hospital Southampton, University of Southampton
Michael J. Kelso, University of WollongongFollow
Ardeshir Rineh, University of WollongongFollow
Nageshwar Rao Yepuri, University of WollongongFollow
Ben Nicholas, University of Southampton, University Hospital Southampton
Laurie Lau, University of Southampton, University Hospital Southampton
David Johnston, University of Southampton, University Hospital Southampton
Peter Lackie, University Hospital Southampton, University of Southampton
Saul Faust, University of Southampton, University Hospital Southampton, Wellcome Trust Clinical Research Facility
Jane Lucas, University of Southampton, University Hospital Southampton
Luanne Hall-Stoodley, University of Southampton, Ohio State University, Wellcome Trust Clinical Research Facility, University Hospital Southampton

RIS ID

116652

Publication Details

Walker, W. T., Jackson, C. L., Allan, R. N., Collins, S. A., Kelso, M. J., Rineh, A., Yepuri, N. R., Nicholas, B., Lau, L., Johnston, D., Lackie, P., Faust, S. N., Lucas, J. S. A. & Hall-Stoodley, L. (2017). Primary ciliary dyskinesia ciliated airway cells show increased susceptibility to Haemophilus influenzae biofilm formation. European Respiratory Journal, 50 (3), 1700612-1-1700612-12.

Abstract

Non-typeable Haemophilus influenzae (NTHi) is the most common pathogen in primary ciliary dyskinesia (PCD) patients. We hypothesised that abnormal ciliary motility and low airway nitric oxide (NO) levels on airway epithelial cells from PCD patients might be permissive for NTHi colonisation and biofilm development. We used a primary epithelial cell co-culture model to investigate NTHi infection. Primary airway epithelial cells from PCD and non-PCD patients were differentiated to ciliation using an air-liquid interface culture and then co-cultured with NTHi. NTHi adherence was greater on PCD epithelial cells compared to non-PCD cells ( p < 0.05) and the distribution of NTHi on PCD epithelium showed more aggregated NTHi in biofilms (p < 0.001). Apart from defective ciliary motility, PCD cells did not significantly differ from non-PCD epithelial cells in the degree of ciliation and epithelial integrity or in cytokine, LL-37 and NO production. Treatment of PCD epithelia using exogenous NO and antibiotic significantly reduced NTHi viability in biofilms compared with antibiotic treatment alone. Impaired ciliary function was the primary defect in PCD airway epithelium underlying susceptibility to NTHi biofilm development compared with non-PCD epithelium. Although NO responses were similar, use of targeted NO with antibiotics enhanced killing of NTHi in biofilms, suggesting a novel therapeutic approach.