Pseudomonas aeruginosa influences the inflammatory response of primary bronchial epithelial cells to rhinovirus infection

Abstract

Chronic pulmonary Pseudomonas aeruginosa (PA) infections affect the majority of adult cystic fibrosis (CF) patients. Respiratory viruses are suggested to trigger pulmonary exacerbations in CF, yet it is unclear if chronic PA infection affects the susceptibility of the airway epithelium and its response to viruses. To investigate interactions between PA and human rhinovirus (HRV), primary bronchial epithelial cells (pBECs) from CF and emphysema patients were cultured as air-liquid interface cultures. Chronic infection with clinical PA isolates was carried out for a total period of 20 days in the presence of low-dose tobramycin. Subsequently, cells were infected with HRV. Key cytokines and viral RNA were quantified by cytometric bead array and qPCR. HRV infection alone increased concentrations of IL-6 (mean±SD: 2301±1873 vs. 16±13 pg/ml) and IL-8 levels (8.2±5.6 vs. 3.2±1.3 ng/ml) and to similar extent in cells co-infected with a mucoid PA isolate. Co-infection with a non-mucoid PA isolate drastically decreased IL-6 protein (51.7±60.4 pg/ml) but not IL-6 mRNA, and increased IL-1s concentrations (33.3±13.3 vs. 3.1±4.5 pg/ml) compared with virus infection alone. IL-8, IP-10, and TNF-α protein, and IFN-s and -λ1 mRNA, as well as viral load did not differ between virus-infected and co-infected cells. We could not detect significant differences in these readouts between emphysema and CF-cells. These data show that PA infection can change the response of pBECS to viral infection. Understanding the interactions between chronic bacterial infection and respiratory viruses could potentially improve management of virus-induced exacerbations in PA-infected CF-patients.