The DOI matches its Crossref record; 61 of the 62 references it cites were found in a registry or an index.
Tumor Progression Locus 2 (Map3k8) Is Critical for Host Defense against Listeria monocytogenes and IL-1β Production
Open accessAbstract
Tumor progression locus 2 (Tpl2, also known as Map3k8 and Cot) is a serine-threonine kinase critical in innate immunity, linking toll-like receptors (TLRs) to TNF production through its activation of ERK. Tpl2−/− macrophages have abrogated TNF production but overproduce IL-12 in response to TLR ligands. Despite enhanced IL-12 production, Tpl2−/− T cells have impaired IFN-γ production. Therefore, the role of Tpl2 in a bona fide bacterial infection where all of these cytokines are important in host defense is unclear. To address this issue, we infected Tpl2−/− mice with the model pathogen Listeria monocytogenes. We found that Tpl2−/− mice infected i.v. with L. monocytogenes had increased pathogen burdens compared with wild-type mice and rapidly succumbed to infection. Enhanced susceptibility correlated with impaired signaling through TLR2 and nucleotide-binding oligomerization domain 2, two receptors previously shown to mediate Listeria recognition. Surprisingly, TNF production in response to infection was not significantly impaired, even though Tpl2 has been implicated in the regulation of TNF. We found that the role of Tpl2 has cell-type specific effects in regulating TNF and transduces signals from some, but not all, pattern recognition receptors (PRR). In contrast to the cell-type- and receptor-specific regulation of TNF, we found that Tpl2 is essential for IL-1β production from both macrophages and dendritic cells. These studies implicate Tpl2 as an important mediator for collaboration of pattern recognition receptors with danger-associated molecular patterns to induce TNF and IL-1β production and optimal host defense.
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“Map3k7 and Map3k8 genes were highly upregulated and were essential for macrophage bacterial killing [47,48], respectively.”
From Trained Immunity Provides Long-Term Protection against Bacterial Infections in Channel Catfish (2022) · cites this paper as [48]
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Cites
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Metadata
- Authors
- Mielke, L. A., Elkins, K. L., Wei, L., Starr, R., Tsichlis, P. N., O'Shea, J. J., & Watford, W. T.
- Affiliations
- National Institutes of Health (US)
- Center for Biologics Evaluation and Research (US)
- St Vincents Institute of Medical Research (AU)
- Tufts Medical Center (US)
- Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health Bethesda , MD 20892
- Corresponding author
- Wei, Lai
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-12
- Volume
- 183
- Issue
- 12
- Pages
- 7984-7993
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC2946069
- OpenAlex
- W2130201289
- Cited by
- 98
- References
- 62
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 8 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 13 · 2016: 11 · 2015: 5 · 2014: 12 · 2013: 7 · 2012: 8
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Office of Science
- National Cancer Institute (R01CA095431)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (#1 K22 AR53953-01, Z01AR041132, ZIAAR041161, Z01AR041159, K22AR053953, Z01AR041160, ZIAAR041167, ZIAAR041106, Z01AR041106, Z01AR041167, ZIAAR041159)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- TPL2, MAP3K8, Listeria monocytogenes, IL-1β, TNF production, TLR2, NOD2, pattern recognition receptors, innate immunity, macrophages, dendritic cells, interferon-gamma, bacterial infection susceptibility, damage-associated molecular patterns
- MeSH terms
- Animals, Cells, Cultured, Female, Gene Expression Regulation, Immunity, Innate, Listeriosis, Listeria monocytogenes, Male, Mice, Inbred C57BL, Proto-Oncogene Proteins, Transduction, Genetic, Signal Transduction, Mice, Knockout, MAP Kinase Kinase Kinases, Mice, Interleukin-1beta
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