التفاصيل البيبلوغرافية
| العنوان: |
Butyrate and propionate are microbial danger signals that activate the NLRP3-inflammasome in human macrophages in the presence of TLR stimulation |
| المؤلفون: |
Wang, Wei, Dernst, Alesja, Martin, Bianca, Lorenzi, Lucia, Cadefau, Maria, Phulphagar, Kshiti, Wagener, Antonia, Budden, Christina, Stair, Neil, Wagner, Theresa, Färber, Harald, Jaensch, Andreas, Stahl, Rainer, Duthie, Fraser, Schmidt, Susanne V., Coll, Rebecca C., Meissner, Felix, Cuartero, Sergi, Latz, Eicke, Mangan, Matthew S.J. |
| المصدر: |
Cell Reports; 20240101, Issue: Preprints |
| مستخلص: |
Short chain fatty acids (SCFAs) are immunomodulatory compounds produced by the microbiome through dietary fibre fermentation. Although generally considered beneficial for gut health, patients suffering from inflammatory bowel disease (IBD) display poor tolerance to fibre-rich diets, suggesting that SCFAs may have contrary effects under inflammatory conditions. To investigate this, we examined the effect of SCFAs on human macrophages in the presence of toll-like receptor agonists. In contrast to anti-inflammatory effects under steady state conditions, we found that butyrate and propionate activated the NLRP3 inflammasome in the presence of TLR agonists. Mechanistically, these SCFAs prevented transcription of cFLIP and IL-10 through HDAC inhibition, triggering caspase-8-dependent NLRP3-inflammasome activation. SCFA-driven NLRP3 activation was potassium efflux independent and did not result in cell death but rather triggered hyperactivation and IL-1β release. Our findings demonstrate that butyrate and propionate are bacterially-derived danger signals that regulate NLRP3 inflammasome activation through epigenetic modulation of the inflammatory response. |
| قاعدة البيانات: |
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