LAUSR

Background: PCD is an inherited heterogenous disorder of impaired mucociliary clearance. Early colonisation of the lower airways with non-typeable Haemophilus influenzae (NTHi) is common. Chronic inflammation and recurrent infections inevitably lead to irreversible bronchiectasis. It is unknown whether epithelial dysfunction contributes to morbidity. We compared the host responses of healthy and PCD respiratory epithelium to NTHi biofilm using proteomic approaches. Method: Nasal epithelial cells were cultured from 5 PCD subjects with DNAH11 mutations and 3 healthy volunteers. Differentiated ciliated cells were co-cultured with a clinical isolate of NTHi for 72 hours in order to colonise the epithelium with biofilm. Following Label-free LC/MS proteomic analyses, proteins were analysed using the Gene Ontology (GO) PANTHER analysis tool. Results: Differences in protein expression between PCD and healthy epithelial cells included upregulation of the following pathways in PCD: “sodium ion export from cell” (adjusted p=0.045) and “cell-cell adhesion” (adj p=0.001). Downregulated PCD pathways were “positive regulation of substrate adhesion-dependent cell spreading” (adj p=0.020) and “cytoskeletal organisation” (adj p Conclusions: We found epithelial dysfunction in PCD in the form of aberrant responses to colonising NTHi. Our data provide potential mechanistic insights into this dysfunction.