Pulmonary constituent cells shape migration patterns of phagocyte cells in staphylococcal pneumonia

Pneumonia caused by the bacterium Staphylococcus aureus can vary in severity, from milder to necrotizing cases. In Staphylococcal pneumonia the cooperative actions of pathogen- and host-derived factors that contribute to disease progression and severity are relatively unknown. The objective of this project is to substantially deepening the understanding of the pathophysiology of Staphylococcal pneumonia, by pin-pointing key host and bacterial factors that contribute to the inflammatory reactions and that are targetable in new therapeutic strategies. The hypothesis is that S. aureus toxins, in addition to have cytotoxic properties, also trigger pulmonary epithelial cells and fibroblasts in ways leading to aggravation of inflammation and pathology. In this study, a complex three-dimensional model of airway epithelium combined with live cell imaging was used to delineate tissue responses to specific staphylococcal toxins. Tissue models were exposed to exotoxins produced by clinical isolates of S. aureus . At sublytic concentrations of toxins, inflammatory responses were induced and chemotactic gradients defined by the redistribution of CXCL8 and CX3CL1 were evident. This coincided with enhanced migration of phagocyte cells towards the apical side of the pulmonary epithelium. Using this innovative model of bacterial infection of the airway epithelium, has the potential to pinpoint novel disease traits and identify new potential targets for treatment aimed at managing detrimental inflammatory reactions.