Joshi Manish, Viallat-Lieutaud Annelise, Royet Julien
Aix-Marseille Université, CNRS, IBDM-UMR7288, Turing Center for Living Systems, 13009 Marseille, France.
iScience. 2023 Jul 10;26(8):107335. doi: 10.1016/j.isci.2023.107335. eCollection 2023 Aug 18.
Interactions between prokaryotes and eukaryotes require a dialogue between MAMPs and PRRs. In bacterial peptidoglycan is detected by PGRP receptors. While the components of the signaling cascades activated upon PGN/PGRP interactions are well characterized, little is known about the subcellular events that translate these early signaling steps into target gene transcription. Using a enteric infection model, we show that gut-associated bacteria can induce the formation of intracellular PGRP-LE aggregates which colocalized with the early endosome marker Rab5. Combining microscopic and RNA-seq analysis, we demonstrate that RNAi inactivation of the endocytosis pathway in the gut affects the expression of essential regulators of the NF-κB response leading not only to a disruption of the immune response locally in the gut but also at the systemic level. This work sheds new light on the involvement of the endocytosis pathway in the control of the gut response to intestinal bacterial infection.
原核生物与真核生物之间的相互作用需要MAMP与PRR之间进行对话。在细菌中，肽聚糖由PGRP受体检测。虽然PGN/PGRP相互作用激活的信号级联成分已得到充分表征，但对于将这些早期信号步骤转化为靶基因转录的亚细胞事件却知之甚少。利用肠道感染模型，我们发现肠道相关细菌可诱导细胞内PGRP-LE聚集体的形成，这些聚集体与早期内体标记物Rab5共定位。结合显微镜和RNA测序分析，我们证明肠道内吞作用途径的RNAi失活会影响NF-κB反应关键调节因子的表达，不仅导致肠道局部免疫反应的破坏，还会影响全身水平的免疫反应。这项工作为内吞作用途径在控制肠道对肠道细菌感染反应中的作用提供了新的见解。
