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AuthorBat-Erdene, Jugder
AuthorKamareddine, Layla
AuthorWatnick, Paula I.
Available date2021-07-07T05:22:55Z
Publication Date2021-06-08
Publication NameImmunity
Identifierhttp://dx.doi.org/10.1016/j.immuni.2021.05.017
CitationJugder et al., Microbiota-derived acetate activates intestinal innate immunity via the Tip60 histone acetyltransferase complex, Immunity (2021), https://doi.org/10.1016/j.immuni.2021.05.017
ISSN10747613
URIhttps://www.sciencedirect.com/science/article/pii/S1074761321002235
URIhttp://hdl.handle.net/10576/21327
AbstractMicrobe-derived acetate activates the Drosophila immunodeficiency (IMD) pathway in a subset of enteroendocrine cells (EECs) of the anterior midgut. In these cells, the IMD pathway co-regulates expression of antimicrobial and enteroendocrine peptides including tachykinin, a repressor of intestinal lipid synthesis. To determine whether acetate acts on a cell surface pattern recognition receptor or an intracellular target, we asked whether acetate import was essential for IMD signaling. Mutagenesis and RNA interference revealed that the putative monocarboxylic acid transporter Tarag was essential for enhancement of IMD signaling by dietary acetate. Interference with histone deacetylation in EECs augmented transcription of genes regulated by the steroid hormone ecdysone including IMD targets. Reduced expression of the histone acetyltransferase Tip60 decreased IMD signaling and blocked rescue by dietary acetate and other sources of intracellular acetyl-CoA. Thus, microbe-derived acetate induces chromatin remodeling within enteroendocrine cells, co-regulating host metabolism and intestinal innate immunity via a Tip60-steroid hormone axis that is conserved in mammals.
Languageen
PublisherElsevier
Subjectmonocarboxylic acid transport
acetate
intestinal microbiota
innate immunity
IMD pathway
Tip60
histone acetyltransferase
histone acetylation
ecdysone
ecdysone receptor
Drosophila melanogaster
Vibrio cholerae
TitleMicrobiota-derived acetate activates intestinal innate immunity via the Tip60 histone acetyltransferase complex
TypeArticle
dc.accessType Full Text


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