湖南师大等:Imd-NF-κB通路促进肠道抗菌免疫同时维持屏障完整性

Immunity

5/8/18Article

22.845

影响因子

原标题:细菌感染中的细胞特异性Imd-NF-κB反应同时促进抗菌免疫和肠上皮细胞脱落

① 肠上皮通过细胞脱落和干细胞活化而不断更新,这种更新维持肠屏障完整性;② 在果蝇中,细菌感染激活的Imd-NF-kB通路,不仅诱导抗菌肽(AMP)的表达,而且通过不依赖ROS相关凋亡的机制控制肠上皮细胞(EC)脱落;③ 细菌感染下,lmd通路协同JNK通路特异性诱导EC脱落,并需要降低转录因子GATAe的表达;④ 细胞特异性NF-κB反应能够同时在不同EC群中产生AMP并促进EC脱落;⑤ Imd-NF-κB通路介导AMP产生和维持屏障完整性,对肠道抗菌反应至关重要。

肠道免疫 肠道屏障 肠上皮细胞 抗菌肽 细菌感染 Imd-NF-κB通路

图片

Title:
Cell-Specific Imd-NF-κB Responses Enable Simultaneous Antibacterial Immunity and Intestinal Epithelial Cell Shedding upon Bacterial Infection

DOI:
10.1016/j.immuni.2018.04.010

Abstract & Authors展开

Abstract:
Intestinal infection triggers potent immune responses to combat pathogens and concomitantly drives epithelial renewal to maintain barrier integrity. Current models propose that epithelial renewal is primarily driven by damage caused by reactive oxygen species (ROS). Here we found that in Drosophila, the Imd-NF-κB pathway controlled enterocyte (EC) shedding upon infection, via a mechanism independent of ROS-associated apoptosis. Mechanistically, the Imd pathway synergized with JNK signaling to induce epithelial cell shedding specifically in the context of bacterial infection, requiring also the reduced expression of the transcription factor GATAe. Furthermore, cell-specific NF-κB responses enabled simultaneous production of antimicrobial peptides (AMPs) and epithelial shedding in different EC populations. Thus, the Imd-NF-κB pathway is central to the intestinal antibacterial response by mediating both AMP production and the maintenance of barrier integrity. Considering the similarities between Drosophila Imd signaling and mammalian TNFR pathway, our findings suggest the existence of an evolutionarily conserved genetic program in immunity-induced epithelial shedding.

All Authors:
Zongzhao Zhai, Jean-Philippe Boquete, Bruno Lemaitre

First Authors:
Zongzhao Zhai

Correspondence:
Zongzhao Zhai, Bruno Lemaitre

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