Aix-Marseille Université, CNRS, IBDM-UMR7288, Turing Center for Living Systems, Marseille, France.
PLoS Genet. 2022 Mar 4;18(3):e1010098. doi: 10.1371/journal.pgen.1010098. eCollection 2022 Mar.
Bacteria that colonize eukaryotic gut have profound influences on the physiology of their host. In Drosophila, many of these effects are mediated by adipocytes that combine immune and metabolic functions. We show here that enteric infection with some bacteria species triggers the activation of the SREBP lipogenic protein in surrounding enterocytes but also in remote fat body cells and in ovaries, an effect that requires insulin signaling. We demonstrate that by activating the NF-κB pathway, the cell wall peptidoglycan produced by the same gut bacteria remotely, and cell-autonomously, represses SREBP activation in adipocytes. We finally show that by reducing the level of peptidoglycan, the gut born PGRP-LB amidase balances host immune and metabolic responses of the fat body to gut-associated bacteria. In the absence of such modulation, uncontrolled immune pathway activation prevents SREBP activation and lipid production by the fat body.
定植于真核生物肠道的细菌对宿主的生理机能有深远影响。在果蝇中，许多此类影响是通过兼具免疫和代谢功能的脂肪体细胞介导的。我们在此展示，肠道内的某些细菌感染会触发周围的肠细胞以及远处的脂肪体细胞和卵巢中 SREBP 脂质生成蛋白的激活，这一效应需要胰岛素信号。我们证明，由同样的肠道细菌产生的细胞壁肽聚糖通过远程和细胞自主的方式激活 NF-κB 通路，从而抑制脂肪细胞中 SREBP 的激活。最后我们表明，通过降低肽聚糖的水平，肠道来源的 PGRP-LB 氨肽酶可平衡脂肪体细胞对肠道相关细菌的宿主免疫和代谢反应。如果没有这种调节，不受控制的免疫途径激活会阻止脂肪体细胞中 SREBP 的激活和脂质的产生。
