Pseudomonas Quinolone Signal Modulates Cystic Fibrosis Epithelial Cell Response through the Toll- Like Receptor 4

Abstract

Pseudomonas aeruginosa is an opportunistic human pathogen that causes severe infection in compromised individuals, including persons with Cystic Fibrosis (CF). The expression of many virulence factors in P. aeruginosa is controlled by Quorum Sensing Molecules (QSMs) that are synthesized and secreted by this bacterium. Recent studies suggest that QSMs are also capable of interspecies communication, with exposure of mammalian cells to Acyl-Homoserine Lactones (AHLs) and Pseudomonas Quinolone Signal (PQS) resulting in an immunomodulatory response. Although the initial immune response is intended to clear/contain the infection, this process is ineffective in CF lungs, and the persistent, excessive inflammation eventually leads to structural damage to the tissue. The goal of this study was to examine the response of IB3-1 CF airway epithelial cell line to PQS, alone and in conjunction with Pseudomonas-Derived Lipopolysaccharides (pLPS). In contrast to results obtained with other cell types suggesting that PQS is anti-inflammatory, PQS induced inflammation in the IB3- 1 CF cell line and exacerbated inflammation when administered simultaneously with LPS, as determined by ELISA for two markers of inflammation, interleukin-6 and interleukin-8. In addition, PQS was shown, for the first time, to act through toll-like receptor 4, a receptor that traditionally has only been associated with LPS. A better understanding of the role that QSMs play in the inflammatory response can potentially lead to new strategies to minimize airway destruction.