Abstract
ChronicP. aeruginosainfections of the respiratory tract pose a major health care problem. The bacterial flagellum represents a tightly regulated virulence factor involved in biofilm formation as well as immune recognition ofP. aeruginosa. Aim of this study was to delineate the role of flagellin using precision-cut lung slices (PCLS) as an organotypic, immunocompetent model of the human lung.
PCLS were prepared from tumour-free lung tissue and infected with wildtype (wt) or flagellin mutant (∆fliC) PA14菌株。持续的我nfection of the tissue over 24h was achieved by treatment with subinhibitory concentrations of tobramycin. Bacterial load was determined and lung tissue viability as well as specific cytokine responses were measured to assess the immune response.
While the initial attachment ofP. aeruginosato the lung tissue was enhanced by the presence of the flagellum, both wt as well as ∆fliCstrains were able to colonize the tissue over 24h. Analysis of cytokine profiles revealed a strong upregulation of pro-inflammatory mediators such as IL-8 (6-fold), IL-6 (6-fold), TNF-α (20-fold), GM-CSF (25-fold), IL-1β (52-fold), and MIP-3α (19-fold) after 24h of infection with wt PA14 compared to non-infected control PCLS. Importantly, infection with ∆fliCPA14 induced 2- to 4-fold lower levels of the respective molecules than the wt strain.
Taken together, we show here that wt as well as flagellar mutantP. aeruginosastrains can infect human lung tissueex vivowhereby flagellin acts as a potent immune stimulus, which could have implications for both immune evasion and biofilm formation ofP. aeruginosa. Future studies will look at the transformation of acute towards persistent infection.
Footnotes
Cite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA5443.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available atwww.ers-education.org(ERS member access only).
- Copyright ©the authors 2019