Effects of influenza A infection on liberation of bacteria from biofilms and inflammatory response in an in vitro model of chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a prevalent and life-altering disease characterized by the persistent inflammation of the sinuses lasting longer than 3 months. <i>Pseudomonas aeruginosa</i> (PA) is a prominent biofilm-forming bacterium that colonizes the sinuses of up to 9% of CRS patients. PA in biofilm exhibits a great resistance to antibiotics and has proven difficult to remove from the sinus mucosa of CRS patients. Influenza A virus (IAV) is the second most common virus detected colonizing CRS patients' sinuses, with previous studies finding that IAV-induced inflammation of human cells causes the dispersal of bacteria encased in biofilms, leading to increased disease exacerbations. Yet, the two pathogens and the effect that co-infection with them has on primary human nasal epithelial cells (HNECs) have to be assessed. In this study, we show that co-infection of HNECs with both clinical and laboratory isolates of PA and with IAV causes no significant change in PA biofilm biomass and no significant change in the production of PA virulence factors. We also show that co-infected HNECs exhibit lower IL-6 response when compared to HNECs infected with IAV alone, suggesting a novel finding where PA is dampening IL-6 response once co-infection occurs.