Lung surfactant protects host against Staphylococcus aureus pathogenesis

Abstract

Lungs are the first organ to encounter aspirated pathogens and have many lines of defense against these diverse invaders. For the most part, these immunological barriers to infection comprised of resident epithelial cells, mucus clearance, and patrolling immune cells are successful in defending the host from infection. Only in cases of viral infections where such a barrier is breached, is an infectious agent more likely to establish an infection. Staphylococcus aureus (S. aureus), found in the anterior nares of more than 20% of the population, is known for causing bacterial lung pneumonia after viral infections like influenza. Previous studies have observed a different pattern of virulence factor gene expression in S. aureus following influenza A virus compared to S. aureus infection only. We hypothesized that either a diseased lung environment triggers S. aureus to be more virulent or the healthy lung naturally suppresses S. aureus colonization. Previous studies have shown that influenza A targets cells producing lung surfactant. In the current study we investigate the influence of surfactant on S. aureus virulence. By assessing S. aureus cytotoxicity against immune cells in the presence of lung surfactant, we discovered that lung surfactant protects host immune cells from S. aureus toxins. To uncover the mechanism behind this protection, we demonstrated that surfactant down-regulated virulence genes regulated by the SaeR/S two-component gene regulatory system. We also investigated one of the more common fatty acids found in lung surfactant, palmitate, for how it impacted S. aureus cytotoxicity and virulence transcription. Palmitate recapitulated the protective phenotype of whole surfactant and modulated S. aureus virulence as seen by cytotoxicity and transcriptional assays. Palmitate was also found to directly act on S. aureus toxins, although the precise mechanism behind this needs to be elucidated. This work provides a rationale for why healthy S. aureus carriers are able to aspirate the bacterium into the lungs and not get primary S. aureus pneumonia. Furthermore, these studies reinforce the potential of surfactant replacement therapy as a treatment or prevention strategy for secondary bacterial pneumonia.