EPS02.3 Pseudomonas aeruginosa and Aspergillus fumigatus co-infection reduced the pro-inflammatory response in CF epithelial cells

Abstract

Objectives Pseudomonas aeruginosa and Aspergillus fumigatus are the most common bacterial and fungal pathogens isolated from cystic fibrosis (CF) airways. This research aims to investigate how these two pathogens interact on the CF airway epithelial cells, contributing to CF lung disease. Methods P. aeruginosa (PA) mucoid/non-mucoid and A. fumigatus (AF) persistent/non-persistent isolates from colonised CF patients were studied. The effect of P. aeruginosa and A. fumigatus co-infection on the host immune response was examined by ELISAs for the pro-inflammatory cytokine IL-8. The signalling pathways involved in this co-infection were investigated employing MAPK inhibitors. Results PA inhibited the growth of AF. AF was capable of growing in the presence of certain PA isolates, suggesting the growth inhibition was strain specific. A greater pro-inflammatory response was observed when the CF epithelial cells were infected with the non-mucoid PA isolates compared to the mucoid isolates. This was also observed when the cells were infected with the non-persistent AF compared to the persistent isolate. A significantly reduced pro-inflammatory response was observed when cells were co-infected with the two pathogens. The co-infection induced IL-8 response occurs via the ERK and p38 MAPK pathways. Conclusion In conclusion PA inhibits the growth of AF. This antifungal activity is exhibited by direct cell contact and not through the release of extracellular secreted molecules. The co-infecting microbes contribute to a reduced inflammatory response which could aid the co-infection to chronically colonise the host which may have detrimental effects on a CF patient's health status.