The stimulation of interferon (IFN)-γ by interleukin (IL)-12 has been shown to provide protection from intracellular pathogens such as Listeria monocytogenes. Tumor necrosis factor (TNF) is also a major player in the resolution of Listeria infections and is suggested to have more global effects than can be explained by the induction of IFN-γ alone. Since IL-18 synergizes with IL-12 to induce IFN-γ production by natural killer and T helper (Th)1 cells, we determined its role in responses to Listeria. IL-18 appeared to be even more potent than either IL-12 or IFN-γ for protection against this pathogen and IL-18 enhanced bacterial clearance in the complete absence of IFN-γ. Indeed IL-18 was comparable to TNF in its ability to resolve the infection and showed a lowered protective capacity in the absence of TNF. Moreover, IL-18 induced macrophages to secrete both TNF and nitric oxide after a Listeria infection. IL-18 was also essential for optimal IFN-γ production by antigen-specific T cells. Therefore, IL-18 operates via its effects on both the innate immune response, including macrophages, as well as on Th1 cells, to protect against Listeria.
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6 August 2001
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August 06 2001
A Critical Role for Interleukin 18 in Primary and Memory Effector Responses to Listeria monocytogenes That Extends Beyond Its Effects on Interferon γ Production
Margaret Neighbors,
Margaret Neighbors
aDepartment of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
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Xiuling Xu,
Xiuling Xu
aDepartment of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
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Franck J. Barrat,
Franck J. Barrat
aDepartment of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
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Sigrid R. Ruuls,
Sigrid R. Ruuls
aDepartment of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
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Tatyana Churakova,
Tatyana Churakova
bDepartment of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
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Reno Debets,
Reno Debets
bDepartment of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
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J. Fernando Bazan,
J. Fernando Bazan
bDepartment of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
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Robert A. Kastelein,
Robert A. Kastelein
bDepartment of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
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John S. Abrams,
John S. Abrams
bDepartment of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
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Anne O'Garra
Anne O'Garra
aDepartment of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
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Margaret Neighbors
aDepartment of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
Xiuling Xu
aDepartment of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
Franck J. Barrat
aDepartment of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
Sigrid R. Ruuls
aDepartment of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
Tatyana Churakova
bDepartment of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
Reno Debets
bDepartment of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
J. Fernando Bazan
bDepartment of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
Robert A. Kastelein
bDepartment of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
John S. Abrams
bDepartment of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
Anne O'Garra
aDepartment of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Incorporated, Palo Alto, CA 94304
Abbreviation used in this paper: HKLM, heat-killed Listeria monocytogenes.
Received:
December 06 2000
Revision Requested:
April 19 2001
Accepted:
April 30 2001
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2001 The Rockefeller University Press
2001
The Rockefeller University Press
J Exp Med (2001) 194 (3): 343–354.
Article history
Received:
December 06 2000
Revision Requested:
April 19 2001
Accepted:
April 30 2001
Citation
Margaret Neighbors, Xiuling Xu, Franck J. Barrat, Sigrid R. Ruuls, Tatyana Churakova, Reno Debets, J. Fernando Bazan, Robert A. Kastelein, John S. Abrams, Anne O'Garra; A Critical Role for Interleukin 18 in Primary and Memory Effector Responses to Listeria monocytogenes That Extends Beyond Its Effects on Interferon γ Production. J Exp Med 6 August 2001; 194 (3): 343–354. doi: https://doi.org/10.1084/jem.194.3.343
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