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
创作:女巫 审核:szx 2018年06月01日
  • 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;
  • 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;
  • 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;
  • 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;
  • 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。
主编推荐语
mildbreeze
肠上皮通过细胞脱落和干细胞活化,进行持续的自我更新,对于维持肠道屏障完整性尤为关键。湖南师大翟宗昭与瑞士洛桑联邦理工大学合作发现,果蝇中,细菌感染激活的Imd-NF-κB通路,是肠道抗菌免疫中的“多面手”,不仅能诱导抗菌肽的表达,还能调控上皮细胞脱落维持肠道屏障,这种机制可能具有进化保守性。相关成果上周在Immunity[IF:22.845]发表,值得关注。
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Immunity [IF:22.553]

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

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

10.1016/j.immuni.2018.04.010

2018-05-08, Article

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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.

First Authors:
Zongzhao Zhai

Correspondence Authors:
Zongzhao Zhai,Bruno Lemaitre

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

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