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

Cell Host Microbe. 2012 Jan 19;11(1):70-80. doi: 10.1016/j.chom.2011.12.004.


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

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Bacterial Toxins / antagonists & inhibitors*
  • Body Temperature
  • Body Weight
  • Cell Line
  • Cell Survival
  • Disease Models, Animal
  • Epithelial Cells / immunology
  • Epithelial Cells / microbiology
  • Hemolysin Proteins / antagonists & inhibitors*
  • Humans
  • Interferon-alpha / immunology*
  • Lipoylation
  • Mice
  • Mice, Knockout
  • Phospholipid Transfer Proteins / metabolism*
  • Protein Processing, Post-Translational
  • Staphylococcal Infections / mortality
  • Staphylococcal Infections / pathology
  • Staphylococcus aureus / immunology*
  • Staphylococcus aureus / pathogenicity*
  • Survival Analysis


  • Bacterial Toxins
  • Hemolysin Proteins
  • Interferon-alpha
  • PLSCR1 protein, human
  • Phospholipid Transfer Proteins
  • staphylococcal alpha-toxin
  • Adenosine Triphosphate