Staphylococcus aureus Lipoteichoic Acid has a Dual Effect on Inflammatory Responses in Airway Epithelial Cells via the Transcription Factor NFκB

Author(s): Clare M Cooksley, Hai Bac Tran, Alkis J Psaltis, Susan Lester, Peter-John Wormald, Sarah Vreugde

Staphylococcus aureus is a major human pathogen that causes a wide array of infections ranging in severity from mild skin infections to life-threatening diseases such as sepsis. S. aureus can cause severe inflammation whilst, at the same time, modulating specific innate and humoral immune defense mechanisms. Lipoteichoic acid (LTA) is a component of the cell wall of gram-positive bacteria that is abundantly released by S. aureus. We investigated the dose-dependent effects of LTA on inflammation in airway epithelial cells. Purified S. aureus LTA was applied to airway epithelial (NuLi-1) cells in a range of concentrations, followed by assessment of expression of NFκB p50 and p65/RelA via qPCR, immunofluorescence and western blot. Multiplex analysis of cell culture supernatants was carried out to evaluate cytokine levels. NFκB p50 mRNA varied according to the LTA dose (p = 0.013) whereas NFκB p65/RelA did not (p = 0.90). A dose-dependent increase in NFκB p50 mRNA expression was seen up to 10 μg/ml LTA treatment, before falling at the 100μg/ml treatment. Western blot analysis showed nuclear and cytoplasmic NFκB p50 and cytoplasmic NFκB p65 protein reduced with increasing LTA concentrations. Multiplex analysis demonstrated that cytokine levels increased with LTA dose, but then decreased at the highest LTA dose (100 μg/ml). This study identifies LTA as having a dual dose-dependent effect on immune activation at low dosages and ablation at high dosages, associated with altered expression levels of NFκB. It adds LTA to the extensive repertoire of possible immune modulators produced by S. aureus.