Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Listeria monocytogenes is widely used as a model to study immune responses against intracellular bacteria. It has been shown that neutrophils and macrophages play an important role to restrict bacterial replication in the early phase of primary infection in mice, and that the cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) are essential for protection. However, the involved signaling pathways and effector mechanisms are still poorly understood. This study investigated mouse strains deficient for the IFN-dependent transcription factors interferon consensus sequence binding protein (ICSBP), interferon regulatory factor (IRF) 1 or 2 for their capacity to eliminate Listeria in vivo and in vitro and for production of inducible reactive nitrogen intermediates (RNI) or reactive oxygen intermediates (ROI) in macrophages. ICSBP-/- and to a lesser degree also IRF2-/- mice were highly susceptible to Listeria infection. This correlated with impaired elimination of Listeria from infected peritoneal macrophage (PEM) cultures stimulated with IFN-gamma in vitro; in addition these cultures showed reduced and delayed oxidative burst upon IFN-gamma stimulation, whereas nitric oxide production was normal. In contrast, mice deficient for IRF1 were not able to produce nitric oxide, but they efficiently controlled Listeria in vivo and in vitro. These results indicate that (a) the ICSBP/IRF2 complex is essential for IFN-gamma-mediated protection against Listeria and that (b) ROI together with additional still unknown effector mechanisms may be responsible for the anti-Listeria activity of macrophages, whereas IRF1-induced RNI are not limiting.

Original publication

DOI

10.1084/jem.185.5.921

Type

Journal article

Journal

J Exp Med

Publication Date

03/03/1997

Volume

185

Pages

921 - 931

Keywords

Adoptive Transfer, Animals, Carrier Proteins, Cell Transplantation, Cells, Cultured, DNA-Binding Proteins, Disease Susceptibility, Immunity, Innate, Interferon Regulatory Factor-1, Interferon Regulatory Factor-2, Interferon Regulatory Factors, Interferon-gamma, Listeriosis, Liver, Macrophages, Peritoneal, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Models, Biological, Nitric Oxide, Phosphoproteins, Reactive Oxygen Species, Repressor Proteins, Respiratory Burst, Signal Transduction, Species Specificity, Spleen, Transcription Factors