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The Drosophila Immune Deficiency Pathway Modulates Enteroendocrine Function and Host Metabolism.
Cell Metabolism ( IF 27.7 ) Pub Date : 2018-Sep-04 , DOI: 10.1016/j.cmet.2018.05.026
Layla Kamareddine , William P. Robins , Cristin D. Berkey , John J. Mekalanos , Paula I. Watnick

Enteroendocrine cells (EEs) are interspersed between enterocytes and stem cells in the Drosophila intestinal epithelium. Like enterocytes, EEs express components of the immune deficiency (IMD) innate immune pathway, which activates transcription of genes encoding antimicrobial peptides. The discovery of large lipid droplets in intestines of IMD pathway mutants prompted us to investigate the role of the IMD pathway in the host metabolic response to its intestinal microbiota. Here we provide evidence that the short-chain fatty acid acetate is a microbial metabolic signal that activates signaling through the enteroendocrine IMD pathway in a PGRP-LC-dependent manner. This, in turn, increases transcription of the gene encoding the endocrine peptide Tachykinin (Tk), which is essential for timely larval development and optimal lipid metabolism and insulin signaling. Our findings suggest innate immune pathways not only provide the first line of defense against infection but also afford the intestinal microbiota control over host development and metabolism.

中文翻译:

果蝇免疫缺陷途径调节肠内分泌功能和宿主代谢。

肠内分泌细胞(EEs)散布在果蝇肠上皮的肠上皮细胞和干细胞之间。EEs像肠细胞一样,表达免疫缺陷(IMD)固有免疫途径的成分,该成分激活编码抗菌肽的基因的转录。在IMD途径突变体的肠道中发现大的脂质滴促使我们研究IMD途径在宿主对其肠道菌群的代谢反应中的作用。在这里,我们提供了证据,即短链脂肪酸乙酸酯是一种微生物代谢信号,可通过依赖于PGRP-LC的肠内分泌IMD途径激活信号传导。反过来,这会增加编码内分泌肽速激肽(Tk)的基因的转录,这对于及时的幼体发育以及最佳的脂质代谢和胰岛素信号传递至关重要。我们的发现表明,先天性免疫途径不仅为抵抗感染提供了第一道防线,而且还为宿主的发育和代谢提供了肠道菌群控制。
更新日期:2018-06-22
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