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IL-1 β is required for IL-12 to induce production of IFN-γ by NK cells. A role for IL-1 β in the T cell-independent mechanism of resistance against intracellular pathogens
Abstract
Mice with the severe combined immunodeficiency (SCID) possess an IFN-gamma-dependent mechanism of resistance to the intracellular pathogens Toxoplasma gondii and Listeria monocytogenes that is dependent on IL-12-induced production of IFN-gamma by NK cells. In this report we demonstrate that IL-1 beta is required for IL-12 to stimulate production of IFN-gamma by NK cells, and that IL-1 is important in IL-12-mediated resistance to T. gondii in vivo. Stimulation of SCID mouse splenocytes with tachyzoites of T. gondii resulted in production of IFN-gamma. Addition of neutralizing Ab specific for IL-1 beta to these cultures inhibited completely the production of IFN-gamma. Similar results were obtained when LPS or L. monocytogenes were used to stimulate production of IFN-gamma by SCID mouse splenocytes. Addition of a neutralizing Ab to IL-1 alpha did not affect production of IFN-gamma by SCID mouse splenocytes stimulated with T. gondii, L. monocytogenes, or LPS. Stimulation of SCID mouse splenocytes with IL-1 beta or IL-1 alpha did not result in production of IFN-gamma but enhanced remarkably the ability of T. gondii or IL-12 to stimulate production of IFN-gamma. Furthermore, production of IFN-gamma by SCID mouse splenocytes stimulated with IL-12 plus TNF-alpha was completely ablated by anti-IL-1 beta, but not by anti-IL-1 alpha. Analysis of the culture supernatants of spleen cells from SCID mice stimulated with T. gondii or IL-12 plus TNF-alpha detected low levels of IL-1 beta; ad…
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“TLR4 signaling is key in driving proinflammatory responses associated with COVID-19 and contributes to an increased Th1-type immune response because IL-18 (and IL-1 β ) strongly induces IFNs. 143-145”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [143]
In the citing paper
“IL-18, originally named IFNγ -inducing factor, strongly drives Th1 immune responses, 143-145 but in BALB/c mice, this produces a mixed Th1/Th2 response that promotes fibrosis and DCM rather than a classical STAT-driven Th1 respo nse. 115,146,160,165”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [143]
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Interleukin-12 and the regulation of innate resistance and adaptive immunity
Trinchieri, G. (2003) · Nature reviews. Immunology · doi:10.1038/nri1001 · Cited by 4,007
Caspase-1 processes IFN-γ-inducing factor and regulates LPS-induced IFN- γ production
Ghayur, T., Banerjee, S., Hugunin, M., Butler, D., Herzog, L., Carter, A. B., Quintal, L. J., Sekut, L., Talanian, R. V., Paskind, M. P., et al. (1997) · Nature · doi:10.1038/386619a0 · Cited by 1,204
IL-18: A TH1 -inducing, proinflammatory cytokine and new member of the IL-1 family
Dinarello, C. A. (1999) · Journal of Allergy and Clinical Immunology · doi:10.1016/s0091-6749(99)70518-x · Cited by 817
Interleukin-12: A Cytokine at the Interface of Inflammation and Immunity
Trinchieri, G. (1998) · Advances in Immunology · doi:10.1016/s0065-2776(08)60387-9 · Cited by 760
Regulation and Function of T-Cell-Mediated Immunity duringToxoplasma gondiiInfection
Denkers, E., & Gazzinelli, R. T. (1998) · Clinical Microbiology Reviews · doi:10.1128/cmr.11.4.569 · Cited by 690
Metadata
- Authors
- Hunter, C. A., Chizzonite, R., & Remington, J. S.
- Affiliations
- Palo Alto Medical Foundation (US)
- ORCID
- Hunter, C A
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1995-11-01
- Volume
- 155
- Issue
- 9
- Pages
- 4347-4354
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2149673255
- Cited by
- 245
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 12 · 2019: 6 · 2018: 3 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 10 · 2013: 9 · 2012: 8
- FWCI
- 6.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI 04717, AI30320)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IL-1β, IL-12, interferon-gamma, natural killer cells, Toxoplasma gondii, Listeria monocytogenes, intracellular pathogens, T cell-independent immunity, IL-1 receptor, IL-1α, TNF-α, SCID mice, infection resistance, cytokine signaling, type I interferon, IL-18
- MeSH terms
- Adjuvants, Immunologic, Animals, Female, Immunity, Innate, Interferon-gamma, Interleukin-1, Killer Cells, Natural, Lipopolysaccharides, Listeria monocytogenes, Spleen, Toxoplasma, Toxoplasmosis, Animal, Mice, SCID, Interleukin-12, Mice
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