RSV Mediates Pseudomonas aeruginosa Binding to Cystic Fibrosis and Normal Epithelial Cells

Abstract

Cystic fibrosis lung disease typically has a course of exacerbations and remissions, suggesting that external factors like viral infections can influence this course. Clinical data suggest synergism between respiratory syncytial virus (RSV) infections and Pseudomonas aeruginosa in cystic fibrosis (CF) lung disease. We studied the influence of RSV infection on adherence of P. aeruginosa to IB3-1, HEp-2, and A549 epithelial cell monolayers in vitro. RSV infection of epithelial cells as well as simultaneous addition of RSV and P. aeruginosa to noninfected cells both strongly enhanced the pseudomonal adherence to epithelial cells. The increased adherence varied from 1.2-to 8.2-fold in case of previous RSV infection, and from 1.7-to 16.1-fold in case of simultaneous addition. We observed direct binding of RSV to P. aeruginosa, and blocking of RSV with heparin eliminated the effect on increased adherence. This suggests that RSV possibly acts as a coupling agent between P. aeruginosa and epithelial cells.

Low Sphingosine-1–Phosphate Impairs Lung Dendritic Cells in Cystic Fibrosis

“…CF mice react with increased inflammation and decreased viral clearance to RSV infection (19). RSV is known to trigger exacerbations of CF lung disease (37)(38)(39) and to facilitate colonization with P. aeruginosa (40). Both cDCs and pDCs are typically activated and increase in number in response to RSV infection (41,42).…”

Viral–bacterial interactions in the respiratory tract

“…Next to increased expression of host receptors, viral proteins displayed on the cell surface can enhance adherence and internalization of bacteria. The RSV attachment glycoprotein (G) protein, present on the surface of either RSV virions or infected cells, can serve as a binding structure for non-typeable H. influenzae (Avadhanula et al, 2007), S. pneumoniae (Avadhanula et al, 2007;Hament et al, 2005) and Pseudomonas aeruginosa (Van Ewijk et al, 2007). Similarly, integration of influenza virus haemagglutinin into the cell membrane of infected cells facilitates attachment and invasive disease of group A streptococci in mice (Okamoto et al, 2003).…”

Innate Immunity of Airway Epithelium and COPD

“…Influenza infection increases risk of secondary bacterial infection by increasing binding or invasion of bacterial pathogen to airway epithelial cells, desensitizing innate immune receptors such as TLRs, and causing immunosuppression by increasing glucocorticosteriod expression (Beadling and Slifka, 2004;Hament et al, 1999;Jamieson et al, 2010;McCullers, 2006;Seki et al, 2004;Sun and Metzger, 2008). Respiratory syncytial virus infection increased persistence of P. aeruginosa in mice and increased P. aeruginosa and NTHi binding to airway epithelial cells (de Vrankrijker et al, 2009;Jiang et al, 1999;Van Ewijk et al, 2007). Respiratory syncytial virus also increased persistence of NTHi by dysregulating the expression of -defensin in chinchilla model of respiratory infection (McGillivary et al, 2009).…”