Role of phospholipid scramblase 1 in type I interferon-induced protection from staphylococcal α-toxin

Staphylococcus aureus is a leading cause of community-acquired and health care-associated pneumonia. The virulence of many clinical isolates of S. aureus correlates with production of α-toxin. This pore-forming toxin contributes to pathogenesis of pneumonia through cytolysis of lung epithelial cells, disruption of lung epithelial barrier, and induction of inflammation. We recently reported that type I IFNs protect lung epithelial cells from the cytolytic action of α-toxin by reducing leakage of cellular ATP into extracellular space. The effect is dependent on induction and protein palmitoylation of phospholipid scramblase 1 (PLSCR1). In IFNα-pretreated cells, PLSCR1 co-localizes with endocytosed α-toxin and associates with cytoskeleton. Depletion of PLSCR1 negates IFN-induced protection from α-toxin and enhances sensitivity to inhaled α-toxin and an α-toxin-producing strain of S. aureus. Here, we discuss the potential implications of these findings.