Phospholipid scramblase 1 mediates type i interferon-induced protection against staphylococcal ?-toxin.

ABSTRACT: The opportunistic gram-positive pathogen Staphylococcus aureus is a leading cause of pneumonia and sepsis. Staphylococcal ?-toxin, a prototypical pore-forming toxin, is a major virulence factor of S. aureus clinical isolates, and lung epithelial cells are highly sensitive to ?-toxin's cytolytic activity. Type I interferon (IFN) signaling activated in response to S. aureus increases pulmonary cell resistance to ?-toxin, but the underlying mechanisms are uncharacterized. We show that IFN? protects human lung epithelial cells from ?-toxin-induced intracellular ATP depletion and cell death by reducing extracellular ATP leakage. This effect depends on protein palmitoylation and induction of phospholipid scramblase 1 (PLSCR1). IFN?-induced PLSCR1 associates with the cytoskeleton after exposure to ?-toxin, and cellular depletion of PLSCR1 negates IFN-induced protection from ?-toxin. PLSCR1-deficient mice display enhanced sensitivity to inhaled ?-toxin and an ?-toxin-producing S. aureus strain. These results uncover PLSCR1 activity as part of an innate protective mechanism to a bacterial pore-forming toxin.

SUBMITTER: Lizak M 

PROVIDER: S-EPMC3266557 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature