Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming

By A. Christ, Patrick Günther, M. Lauterbach, P. Duewell, Debjani Biswas, K. Pelka, C. Scholz, M. Oosting, Kristian Haendler, K. Bassler and 16 more. Cell, 2018

946 citations recorded by the source corpus.

SUMMARY Long-term epigenetic reprogramming of innate immune cells in response to microbes, also termed “trained immunity,” causes prolonged altered cellular functionality to protect from secondary infections. Here, we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (WD) feeding of Ldlr−/− mice induced systemic inflammation, which was undetectable in serum soon after mice were shifted back to a chow diet (CD). In contrast, myeloid cell responses toward innate stimuli remained broadly augmented. WD-induced transcriptomic and epigenomic reprogramming of myeloid progenitor cells led to increased proliferation and enhanced innate immune responses. Quantitative trait locus (QTL) analysis in human monocytes trained with oxidized low-density lipoprotein (oxLDL) and stimulated with lipopolysaccharide (LPS) suggested inflammasome-mediated trained immunity. Consistently, Nlrp3−/−/Ldlr−/− mice lacked WD-induced systemic inflammation, myeloid progenitor proliferation, andre-programming. Hence, NLRP3 mediates trained immunity following WD and could thereby mediate the potentially deleterious effects of trained immunity in inflammatory diseases.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/b8dbb2186cd9f701c9d3b961f78e5db2e376a2d4

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In Immunology

1. B. Levy
2. C. Serhan
3. A. Mildner
4. Joachim L. Schultze
5. S. Yona
6. A. Grebe
7. M. Guilliams
8. E. Latz

Citations in the corpus

• Developmental and Functional Heterogeneity of Monocytes. (2018, background): “and splenic myeloid cells produced more inflammatory cytokines upon TLR stimulation compared to control mice (Christ et al., 2018).”
• Human Monocyte Subsets and Phenotypes in Major Chronic Inflammatory Diseases (2019, background): “Furthermore, single nucleotide polymorphisms at the gene regions of the inflammasome adaptor ASC and the IL-1 receptor antagonist were identified to have an effect on the training response of human monocytes to oxLDL which proposes the involvement of the inflammasome in this process (67).”
• Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. (2018, background): “Western diet triggers inflammasome-mediated trained immunity with heightened inflammation (191).”
• NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis. (2018, background): “After 8 weeks of Western diet feeding, Ldlr/Nlrp3 double knockout mice develop significantly reduced atherosclerotic lesion sizes.(159)”
• Dietary Choices and Habits during COVID-19 Lockdown: Experience from Poland (2020, background): “A fast food diet and high consumption of meat products, particularly red and processed red meat, has been associated with pro-inflammatory effects [53,54]; therefore, it seems reasonable that their consumption should not be preferred to vegetables, fruits, and legumes, particularly during a pandemic”
• Metabolic Induction of Trained Immunity through the Mevalonate Pathway. (2018, neutral): “Interestingly, when transcriptome analysis was performed on these cells, several immune signaling pathways and the cholesterol synthesis pathways have been shown to be modulated in trained monocytes (Christ et al., 2018 [this issue of Cell]).”