Microbiota-derived acetate activates intestinal innate immunity via the Tip60 histone acetyltransferase complex.
Microbiota-derived acetate activates intestinal innate immunity via the Tip60 histone acetyltransferase complex.
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微生物来源的醋酸盐通过Tip60组蛋白乙酰转移酶复合物激活肠道先天免疫。
DOI：
10.1016/j.immuni.2021.05.017
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发表时间：
2021-08-10
期刊：
影响因子：
32.4
通讯作者：
Watnick PI
中科院分区：
文献类型：
--
作者：
Jugder BE;Kamareddine L;Watnick PI
微生物来源的醋酸盐激活果蝇前中肠肠内分泌细胞（EEC）亚群中的免疫缺陷（IMD）途径。在这些细胞中，IMD途径共调节抗菌肽和肠内分泌肽的表达，包括速激肽，肠脂质合成的阻遏物。为了确定乙酸盐是否作用于细胞表面模式识别受体或细胞内靶点，我们询问乙酸盐输入是否对IMD信号传导至关重要。突变和RNA干扰表明，推定的单羧酸转运蛋白Tarag是必不可少的增强IMD信号的饮食乙酸。干扰组蛋白去乙酰化增强了由类固醇激素蜕皮激素（包括IMD靶点）调控的基因转录。组蛋白乙酰转移酶Tip 60的表达减少会降低IMD信号传导，并阻断饮食乙酸盐和其他细胞内乙酰辅酶A来源的救援。因此，微生物衍生的乙酸盐诱导肠内分泌细胞内的染色质重塑，通过哺乳动物中保守的Tip 60-类固醇激素轴共调节宿主代谢和肠先天免疫。微生物来源的醋酸盐激活果蝇免疫缺陷（IMD）途径的肠道肠内分泌细胞（EEC）的一个子集，调节抗菌肽和肠内分泌肽的表达。Jugder等人揭示，醋酸盐通过哺乳动物中保守的Tip 60-类固醇激素轴特异性调节Tip 60组蛋白乙酰转移酶复合物的功能，诱导内皮细胞内的染色质重塑。
Microbe-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. Microbe-derived acetate activates the Drosophila Immunodeficiency (IMD) pathway in a subset of intestinal enteroendocrine cells (EECs), which regulates expression of antimicrobial and enteroendocrine peptides. Jugder et al. reveal that acetate induces chromatin remodeling within EECs by specifically modulating the function of the Tip60 histone acetyltransferase complex via a Tip60-steroid hormone axis that is conserved in mammals.
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影响因子：
6.7
作者：
Benguettat O;Jneid R;Soltys J;Loudhaief R;Brun-Barale A;Osman D;Gallet A
通讯作者：
Gallet A
影响因子：
4.6
作者：
Bakshi K;Ranjitha B;Dubey S;Jagannadham J;Jaiswal B;Gupta A
通讯作者：
Gupta A
影响因子：
3.4
作者：
Berkey CD;Blow N;Watnick PI
通讯作者：
Watnick PI
DOI：
10.1073/pnas.0404952102
发表时间：
2005-01-25
影响因子：
11.1
作者：
Choe, KM;Lee, H;Anderson, KV
通讯作者：
Anderson, KV
影响因子：
4.8
作者：
Brady, ME;Ozanne, DM;Robson, CN
通讯作者：
Robson, CN