Interferons increase cell resistance to Staphylococcal alpha-toxin.
Many bacterial pathogens, including Staphylococcus aureus, use a variety of pore-forming toxins as important virulence factors. Staphylococcal alpha-toxin, a prototype beta-barrel pore-forming toxin, triggers the release of proinflammatory mediators and induces primarily necrotic death in susceptible cells. However, whether host factors released in response to staphylococcal infections may increase cell resistance to alpha-toxin is not known. Here we show that prior exposure to interferons (IFNs) prevents alpha-toxin-induced membrane permeabilization, the depletion of ATP, and cell death. Moreover, pretreatment with IFN-alpha decreases alpha-toxin-induced secretion of interleukin 1beta (IL-1beta). IFN-alpha, IFN-beta, and IFN-gamma specifically protect cells from alpha-toxin, whereas tumor necrosis factor alpha (TNF-alpha), IL-6, and IL-4 have no effects. Furthermore, we show that IFN-alpha-induced protection from alpha-toxin is not dependent on caspase-1 or mitogen-activated protein kinases, but requires protein synthesis and fatty acid synthase activity. Our results demonstrate that IFNs may increase cell resistance to staphylococcal alpha-toxin via the regulation of lipid metabolism and suggest that interferons play a protective role during staphylococcal infections.
Yarovinsky
Timur O
TO
Yale University School of Medicine, Department of Immunobiology, TAC S555, 300 Cedar Street, New Haven, CT 06520, USA. timur.yarovinsky@yale.edu
Monick
Martha M
MM
Husmann
Matthias
M
Hunninghake
Gary W
GW
D000255:Adenosine Triphosphate / Q000378:metabolism; D001427:Bacterial Toxins / Q000276:immunology / Q000633:toxicity*; D016923:Cell Death; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D064429:Fatty Acid Synthases / Q000378:metabolism; D006460:Hemolysin Proteins / Q000276:immunology / Q000633:toxicity*; D006801:Humans; D007372:Interferons / Q000276:immunology*; D053583:Interleukin-1beta / Q000378:metabolism; D014176:Protein Biosynthesis; D013211:Staphylococcus aureus / Q000276:immunology* / Q000378:metabolism*
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D053583:Interleukin-1beta; C021091:staphylococcal alpha-toxin; D000255:Adenosine Triphosphate; D007372:Interferons; D064429:Fatty Acid Synthases