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Infection and Immunity, February 2008, p. 571-577, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01088-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Interferons Increase Cell Resistance to Staphylococcal Alpha-Toxin{triangledown}

Timur O. Yarovinsky,1* Martha M. Monick,2 Matthias Husmann,3 and Gary W. Hunninghake2

Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520,1 University of Iowa Carver College of Medicine, Veterans Administration Medical Center, Iowa City, Iowa 52242,2 Institute of Medical Microbiology and Hygiene, Johannes Gutenberg-University Mainz, Mainz, Germany3

Received 6 August 2007/ Returned for modification 18 September 2007/ Accepted 28 November 2007

Many bacterial pathogens, including Staphylococcus aureus, use a variety of pore-forming toxins as important virulence factors. Staphylococcal alpha-toxin, a prototype β-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 1β (IL-1β). IFN-{alpha}, IFN-β, 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.

* Corresponding author. Mailing address: Yale University School of Medicine, Department of Immunobiology, TAC S555, 300 Cedar Street, New Haven, CT 06520. Phone: (203) 785-5320. Fax: (203) 737-1765. E-mail: timur.yarovinsky{at}yale.edu

{triangledown} Published ahead of print on 10 December 2007.

Editor: B. A. McCormick

Infection and Immunity, February 2008, p. 571-577, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01088-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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