ArticleThe Journal of clinical investigation2004
TNF-alpha is a critical negative regulator of type 1 immune activation during intracellular bacterial infection.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
95 citing papers in PubMed, 199 citations in OpenAlex.
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- An impact of type 2 diabetes mellitus on NKT-like cell population in humans: a new insight into impaired immune response in hyperglycemia.Frontiers in endocrinology · 2025Article
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- Surface Topography, Microbial Adhesion, and Immune Responses in Silicone Mammary Implant-Associated Capsular Fibrosis.International journal of molecular sciences · 2024Article
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- Possible Mechanisms of Lymphopenia in Severe Tuberculosis.Microorganisms · 2023Review
- Altered Tumor Necrosis Factor Response in Neurologic Postacute SARS-CoV-2 Syndrome.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Article
- Inhibition of Cyclin-Dependent Kinases 8/19 Restricts Bacterial and Virus-Induced Inflammatory Responses in Monocytes.Viruses · 2023Article
- Who Knew? Dopamine Transporter Activity Is Critical in Innate and Adaptive Immune Responses.Cells · 2023Article
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- TNF blockade enhances the efficacy of myxoma virus-based oncolytic virotherapy.Journal for immunotherapy of cancer · 2022Article
- Distinct Role of TNFR1 and TNFR2 in Protective Immunity AgainstFrontiers in immunology · 2022Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TNF-alpha has long been regarded as a proimmune cytokine involved in antimicrobial type 1 immunity. However, the precise role of TNF-alpha in antimicrobial type 1 immunity remains poorly understood. We found that TNF-alpha-deficient (TNF(-/-)) mice quickly succumbed to respiratory failure following lung infection with replication-competent mycobacteria, because of apoptosis and necrosis of granuloma and lung structure. Tissue destruction was a result of an uncontrolled type 1 immune syndrome characterized by expansion of activated CD4 and CD8 T cells, increased frequency of antigen-specific T cells, and overproduction of IFN-gamma and IL-12. Depletion of CD4 and CD8 T cells decreased IFN-gamma levels, prevented granuloma and tissue necrosis, and prolonged the survival of TNF(-/-) hosts. Early reconstitution of TNF-alpha by gene transfer reduced the frequency of antigen-specific T cells and improved survival. TNF-alpha controlled type 1 immune activation at least in part by suppressing T cell proliferation, and this suppression involved both TNF receptor p55 and TNF receptor p75. Heightened type 1 immune activation also occurred in TNF(-/-) mice treated with dead mycobacteria, live replication-deficient mycobacteria, or mycobacterial cell wall components. Our study thus identifies TNF-alpha as a type 1 immunoregulatory cytokine whose primary role, different from those of other type 1 cytokines, is to keep an otherwise detrimental type 1 immune response in check.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.