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-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) 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-γ in vitro; in addition these cultures showed reduced and delayed oxidative burst upon IFN-γ 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-γ–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.
Skip Nav Destination
Article navigation
3 March 1997
Article|
March 03 1997
Crucial Role of Interferon Consensus Sequence Binding Protein, but neither of Interferon Regulatory Factor 1 nor of Nitric Oxide Synthesis for Protection Against Murine Listeriosis
Thomas Fehr,
Thomas Fehr
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Search for other works by this author on:
Gabriele Schoedon,
Gabriele Schoedon
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Search for other works by this author on:
Bernhard Odermatt,
Bernhard Odermatt
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Search for other works by this author on:
Thomas Holtschke,
Thomas Holtschke
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Search for other works by this author on:
Markus Schneemann,
Markus Schneemann
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Search for other works by this author on:
Martin F. Bachmann,
Martin F. Bachmann
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Search for other works by this author on:
Tak W. Mak,
Tak W. Mak
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Search for other works by this author on:
Ivan Horak,
Ivan Horak
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Search for other works by this author on:
Rolf M. Zinkernagel
Rolf M. Zinkernagel
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Search for other works by this author on:
Thomas Fehr
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Gabriele Schoedon
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Bernhard Odermatt
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Thomas Holtschke
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Markus Schneemann
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Martin F. Bachmann
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Tak W. Mak
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Ivan Horak
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Rolf M. Zinkernagel
From the *Institute of Experimental Immunology, University Hospital, CH-8091 Zürich, Switzerland; ‡Department of Internal Medicine, University Hospital, CH-8091 Zürich, Switzerland; §Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; ‖Department of Molecular Genetics, Research Institute of Molecular Pharmacology, D-12207 Berlin, Germany; and ¶Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario, M4X1K9, Canada
Address correspondence to Thomas Fehr, Institute of Experimental Immunology, University Hospital, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland.
1Abbreviations used in this paper: ICSBP, interferon consensus sequence binding protein; i.f., into the footpad; iNOS, inducible nitric oxide synthase; IRF1/2, interferon regulatory factor 1/2; ISGF, interferon-stimulated gene factor; ISRE, interferon-stimulated response element; NO, nitric oxide; PEM, peritoneal macrophage; RNI, reactive nitrogen intermediates; ROI, reactive oxygen intermediates; STAT, signal transducers and activators of transcription.
Received:
October 21 1996
Revision Received:
December 17 1996
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 185 (5): 921–932.
Article history
Received:
October 21 1996
Revision Received:
December 17 1996
Citation
Thomas Fehr, Gabriele Schoedon, Bernhard Odermatt, Thomas Holtschke, Markus Schneemann, Martin F. Bachmann, Tak W. Mak, Ivan Horak, Rolf M. Zinkernagel; Crucial Role of Interferon Consensus Sequence Binding Protein, but neither of Interferon Regulatory Factor 1 nor of Nitric Oxide Synthesis for Protection Against Murine Listeriosis. J Exp Med 3 March 1997; 185 (5): 921–932. doi: https://doi.org/10.1084/jem.185.5.921
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement
