title: Interferon-γ Protects from Staphylococcal Alpha Toxin-Induced Keratinocyte Death through Apolipoprotein L1.
abstract: Staphylococcus aureus is a bacterial pathogen that frequently infects the skin, causing lesions and cell destruction through its primary virulence factor, alpha toxin. Here we show that interferon gamma (IFN-?) protects human keratinocytes from cell death induced by staphylococcal alpha toxin. We find that IFN-? prevents alpha toxin binding and reduces expression of the alpha toxin receptor, a disintegrin and metalloproteinase 10 (ADAM10). We determine that the mechanism for IFN-?-mediated resistance to alpha toxin involves the induction of autophagy, a process of cellular adaptation to sublethal damage. We find that IFN-? potently stimulates activation of the primary autophagy effector, light chain 3 (LC3). This process is dependent on upregulation of apolipoprotein L1. Depletion of apolipoprotein L1 by small interfering RNA significantly increases alpha toxin-induced lethality and inhibits activation of light chain 3. We conclude that IFN-? plays a significant role in protecting human keratinocytes from the lethal effects of staphylococcal alpha toxin through apolipoprotein L1-induced autophagy.
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, Colorado, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Brauweiler
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, Colorado, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Goleva
authors.affiliation: Department of Pediatrics, National Jewish Health, Denver, Colorado, USA; Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, USA. Electronic address: leungd@njhealth.org.
authors.forename: Donald Y M
authors.initials: DYM
authors.lastname: Leung
mesh_terms: D000704:Analysis of Variance; D001053:Apolipoproteins / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects*; D001427:Bacterial Toxins / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D006460:Hemolysin Proteins / Q000494:pharmacology*; D006801:Humans; D015151:Immunoblotting; D007371:Interferon-gamma / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D013211:Staphylococcus aureus
chemical_list: D001053:Apolipoproteins; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin; D007371:Interferon-gamma