The Immune Receptor NOD1 and Kinase RIP2 Interact with Bacterial Peptidoglycan on Early Endosomes to Promote Autophagy and Inflammatory Signaling

The intracellular innate immune receptor NOD1 detects Gram-negative bacterial peptidoglycan (PG) to induce autophagy and inflammatory responses in host cells. To date, the intracellular compartment in which PG is detected by NOD1 and whether NOD1 directly interacts with PG are two questions that remain to be resolved. To address this, we used outer membrane vesicles (OMVs) from pathogenic bacteria as a physiological mechanism to deliver PG into the host cell cytosol. We report that OMVs induced autophagosome formation and inflammatory IL-8 responses in epithelial cells in a NOD1-and RIP2-dependent manner. PG contained within OMVs colocalized with both NOD1 and RIP2 in EEA1-positive early endosomes. Further, we provide evidence for direct interactions between NOD1 and PG. Collectively, these findings demonstrate that NOD1 detects PG within early endosomes, thereby promoting RIP2-dependent autophagy and inflammatory signaling in response to bacterial infection.

细胞内固有免疫受体NOD1可检测革兰氏阴性菌肽聚糖（PG），从而诱导宿主细胞发生自噬和炎症反应。到目前为止，NOD1在细胞内的哪个区室检测PG以及NOD1是否与PG直接相互作用这两个问题仍有待解决。为了解决这些问题，我们利用病原菌的外膜囊泡（OMVs）作为一种生理机制将PG递送到宿主细胞胞质中。我们发现OMVs以依赖NOD1和RIP2的方式诱导上皮细胞中自噬体的形成以及炎症性白细胞介素 - 8（IL - 8）反应。OMVs中包含的PG与NOD1和RIP2在EEA1阳性早期内体中共定位。此外，我们提供了NOD1与PG直接相互作用的证据。总之，这些研究结果表明，NOD1可检测早期内体中的PG，从而在细菌感染时促进依赖RIP2的自噬和炎症信号传导。