Lung surfactant reduces <i>Staphylococcus aureus</i> cytotoxicity and protects host immune cells from membrane damage

In this study, we identify that lung surfactant significantly reduces the cytotoxicity of <i>Staphylococcus aureus</i> (<i>S. aureus</i>) membrane-damaging toxins. Data demonstrate that natural surfactants from mice and rats and commercially available surfactant, Infasurf, protect human primary cells (neutrophils and peripheral blood mononuclear cells) from cytolytic activity caused by <i>S. aureus</i> supernatants. Supernatants from <i>S. aureus</i> grown in surfactant showed a significant reduction in plasma membrane damage against primary human cells as compared to supernatants grown without surfactant. This reduction was not due to a direct bactericidal effect of the surfactants on <i>S. aureus</i> growth. Rat and mouse surfactants downregulated the gene expression of <i>saeR</i>, the response regulator of the <i>S. aureus</i> two-component system SaeR/S that is responsible for the production of virulence factors which are important during lung infection and cause membrane damage in host cells. Rat and lung surfactants also reduced transcript abundance of SaeR/S-regulated genes <i>lukF</i>-PV, <i>hla</i>, and <i>hlgA</i>. Interestingly, the commercially available surfactant Infasurf did not recapitulate the effect of natural surfactants and did not decrease gene transcription of the virulence genes tested. These data suggest that components of natural surfactants protect lungs from <i>S. aureus</i> by suppressing <i>S. aureus</i> virulence factors and have implications for the role of surfactants in host defense against <i>S. aureus</i>.IMPORTANCEThis study explored the influence of lung surfactants on membrane-damaging <i>Staphylococcus aureus</i> (<i>S. aureus</i>) toxins. We demonstrate that natural and commercially available lung surfactants minimize the cytolytic capacity of <i>S. aureus</i> supernatants against primary human cells. Data indicate that cytolytic reduction by mouse and rat surfactants was partially due to surfactants reducing transcript abundance of virulence factors. This work identifies a novel role for surfactants and suggests their importance in modulating the severity of <i>S. aureus</i> lung infections.