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Infect. Immun. doi:10.1128/IAI.01251-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Stimulation of inducible nitric oxide synthase expression by interferon beta increases necrotic death of macrophages upon Listeria monocytogenes infection

Max-Perutz Laboratories, Vienna Biocenter, Department of Microbiology and Immunobiology, Department of Molecular Cell Biology, University of Vienna, Dr. Bohr-Gasse 9/4, A1030 Vienna, Austria

^* To whom correspondence should be addressed. Email: thomas.decker{at}univie.ac.at.

	Abstract

Murine macrophage death upon infection with Listeria monocytogenes was previously shown to be increased by interferon beta, produced by the infected cells. We saw that interferon-upregulated caspase activation or other interferon-inducible, death associated proteins including TRAIL, PKR, p53 were not necessary for cell death. Macrophage death was reduced when inducible nitric oxide synthase (iNOS) was inhibited during infection, and iNOS-deficient macrophages were less susceptible to death upon infection than wild type cells. The production of nitric oxide correlated with increased death, while no role was seen for iNOS in control of Listeria number during infection of resting macrophages. This indicates that the induction of iNOS by interferon beta in cells infected with L. monocytogenes contributes to cell death. Based on morphology, the maintenance of mitochondrial membrane potential, and a lack of dependence on caspase 1, we characterize the type of cell death occurring and show the infected macrophages die by interferon-upregulated necrosis.