| First Author | Lizak M | Year | 2012 |
| Journal | Cell Host Microbe | Volume | 11 |
| Issue | 1 | Pages | 70-80 |
| PubMed ID | 22264514 | Mgi Jnum | J:210792 |
| Mgi Id | MGI:5571833 | Doi | 10.1016/j.chom.2011.12.004 |
| Citation | Lizak M, et al. (2012) Phospholipid scramblase 1 mediates type i interferon-induced protection against staphylococcal alpha-toxin. Cell Host Microbe 11(1):70-80 |
| abstractText | The opportunistic gram-positive pathogen Staphylococcus aureus is a leading cause of pneumonia and sepsis. Staphylococcal alpha-toxin, a prototypical pore-forming toxin, is a major virulence factor of S. aureus clinical isolates, and lung epithelial cells are highly sensitive to alpha-toxin's cytolytic activity. Type I interferon (IFN) signaling activated in response to S. aureus increases pulmonary cell resistance to alpha-toxin, but the underlying mechanisms are uncharacterized. We show that IFNalpha protects human lung epithelial cells from alpha-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). IFNalpha-induced PLSCR1 associates with the cytoskeleton after exposure to alpha-toxin, and cellular depletion of PLSCR1 negates IFN-induced protection from alpha-toxin. PLSCR1-deficient mice display enhanced sensitivity to inhaled alpha-toxin and an alpha-toxin-producing S. aureus strain. These results uncover PLSCR1 activity as part of an innate protective mechanism to a bacterial pore-forming toxin. |
