Home > Publications Database > Butyrate and propionate are microbial danger signals that activate the NLRP3 inflammasome in human macrophages upon TLR stimulation. > print

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024 7 _ |a 10.1016/j.celrep.2024.114736
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024 7 _ |a 2639-1856
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037 _ _ |a DZNE-2024-01169
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Wang, Wei
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245 _ _ |a Butyrate and propionate are microbial danger signals that activate the NLRP3 inflammasome in human macrophages upon TLR stimulation.
260 _ _ |a [New York, NY]
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336 7 _ |a article
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520 _ _ |a Short-chain fatty acids (SCFAs) are immunomodulatory compounds produced by the microbiome through dietary fiber fermentation. Although generally considered beneficial for gut health, patients suffering from inflammatory bowel disease (IBD) display poor tolerance to fiber-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 (TLR) agonists. In contrast to anti-inflammatory effects under steady-state conditions, we found that butyrate and propionate activated the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in the presence of TLR agonists. Mechanistically, these SCFAs prevented transcription of FLICE-like inhibitory protein (cFLIP) and interleukin-10 (IL-10) through histone deacetylase (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.
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650 _ 7 |a CP: Immunology
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650 _ 7 |a HDAC
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650 _ 7 |a IL-10
|2 Other
650 _ 7 |a NLRP3
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650 _ 7 |a SCFA
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650 _ 7 |a acetylation
|2 Other
650 _ 7 |a butyrate
|2 Other
650 _ 7 |a cFLIP
|2 Other
650 _ 7 |a caspase-8
|2 Other
650 _ 7 |a inflammasome
|2 Other
650 _ 7 |a propionate
|2 Other
650 _ 7 |a NLR Family, Pyrin Domain-Containing 3 Protein
|2 NLM Chemicals
650 _ 7 |a Inflammasomes
|2 NLM Chemicals
650 _ 7 |a Propionates
|2 NLM Chemicals
650 _ 7 |a Butyrates
|2 NLM Chemicals
650 _ 7 |a Toll-Like Receptors
|2 NLM Chemicals
650 _ 7 |a NLRP3 protein, human
|2 NLM Chemicals
650 _ 7 |a Interleukin-1beta
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650 _ 7 |a Interleukin-10
|0 130068-27-8
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650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a NLR Family, Pyrin Domain-Containing 3 Protein: metabolism
|2 MeSH
650 _ 2 |a Inflammasomes: metabolism
|2 MeSH
650 _ 2 |a Propionates: pharmacology
|2 MeSH
650 _ 2 |a Butyrates: pharmacology
|2 MeSH
650 _ 2 |a Macrophages: metabolism
|2 MeSH
650 _ 2 |a Macrophages: drug effects
|2 MeSH
650 _ 2 |a Toll-Like Receptors: metabolism
|2 MeSH
650 _ 2 |a Signal Transduction: drug effects
|2 MeSH
650 _ 2 |a Interleukin-1beta: metabolism
|2 MeSH
650 _ 2 |a Interleukin-10: metabolism
|2 MeSH
700 1 _ |a Dernst, Alesja
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700 1 _ |a Martin, Bianca
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700 1 _ |a Lorenzi, Lucia
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700 1 _ |a Cadefau-Fabregat, Maria
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700 1 _ |a Phulphagar, Kshiti
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700 1 _ |a Wagener, Antonia
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700 1 _ |a Budden, Christina
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700 1 _ |a Stair, Neil
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700 1 _ |a Wagner, Theresa
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700 1 _ |a Färber, Harald
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700 1 _ |a Jaensch, Andreas
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700 1 _ |a Stahl, Rainer
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700 1 _ |a Duthie, Fraser
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700 1 _ |a Schmidt, Susanne V
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700 1 _ |a Coll, Rebecca C
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700 1 _ |a Meissner, Felix
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700 1 _ |a Cuartero, Sergi
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700 1 _ |a Latz, Eicke
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700 1 _ |a Mangan, Matthew
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773 _ _ |a 10.1016/j.celrep.2024.114736
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