ArticleInnate immunity2017
TLR ligands, but not modulators of histone modifiers, can induce the complex immune response pattern of endotoxin tolerance in mammary epithelial cells.
Article in Innate immunity, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- The emerging role of neutrophil extracellular traps in autoimmune and autoinflammatory diseases.MedComm · 2025Review
- Endotoxin-Tolerance Mimicking to Study TLR in Promotion of Tolerogenic DCs and Tr1 Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Non-classical monocytes contribute to innate immune training in cattle.Innate immunity · 2022Article
- Immune defenses of the mammary gland epithelium of dairy ruminants.Frontiers in immunology · 2022Review
- Single-cell RNA sequencing of freshly isolated bovine milk cells and cultured primary mammary epithelial cells.Scientific data · 2021Article
- Intramammary Immunisation Provides Short Term Protection AgainstFrontiers in veterinary science · 2021Article
- The Role of Innate Immune Response and Microbiome in Resilience of Dairy Cattle to Disease: The Mastitis Model.Animals : an open access journal from MDPI · 2020Review
- Activation of a Bovine Mammary Epithelial Cell Line by Ruminant-AssociatedMicroorganisms · 2019Article
- Mammary Defences and Immunity against Mastitis in Sheep.Animals : an open access journal from MDPI · 2019Review
- The first line of defence: insights into mechanisms and relevance of phagocytosis in epithelial cells.Seminars in immunopathology · 2018Review
- Tolerance induced by Porphyromonas gingivalis may occur independently of TLR2 and TLR4.PloS one · 2018Article
- Regulation of Endotoxin Tolerance and Compensatory Anti-inflammatory Response Syndrome by Non-coding RNAs.Frontiers in immunology · 2018Review
- Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excessive stimulation of the TLR4 axis through LPS reduces the expression of some cytokine genes in immune cells, while stimulating the expression of immune defense genes during a subsequent bacterial infection. This endotoxin tolerance (ET) is mediated via epigenetic mechanisms. Priming the udder of cows with LPS was shown to induce ET in mammary epithelial cells (MEC), thereby protecting the udder against reinfection for some time. Seeking alternatives to LPS priming we tried to elicit ET by priming MEC with either lipopeptide (Pam2CSK4) via the TLR2/6 axis or inhibitors of histone-modifying enzymes. Pre-incubation of MEC with Pam2CSK4 enhanced baseline and induced expression of bactericidal (β-defensin; SLPI) and membrane protecting factors ( SAA3, TGM3), while reducing the expression of cytokine- and chemokine-encoding genes ( TNF, IL1β) after a subsequent pathogen challenge, the latter, however, not as efficiently as after LPS priming. Pre-treating MEC with various inhibitors of histone H3 modifiers (for demethylation, acetylation or deacetylation) all failed to induce any of the protective factors and only resulted in some dampening of cytokine gene expression after the re-challenge. Hence, triggering immune functions via the TLR axis, but not through those histone modifiers, induced the beneficial phenomenon of ET in MEC.
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Registered trials
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