論文 - 詳細
| RRC ID | 57364 |
|---|---|
| 著者 | Zhai Z, Boquete JP, Lemaitre B. |
| タイトル | Cell-Specific Imd-NF-κB Responses Enable Simultaneous Antibacterial Immunity and Intestinal Epithelial Cell Shedding upon Bacterial Infection. |
| ジャーナル | Immunity |
| 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. |
| 巻・号 | 48(5) |
| ページ | 897-910.e7 |
| 公開日 | 2018-5-15 |
| DOI | 10.1016/j.immuni.2018.04.010 |
| PII | S1074-7613(18)30179-1 |
| PMID | 29752064 |
| MeSH | Animals Animals, Genetically Modified Antimicrobial Cationic Peptides / immunology* Antimicrobial Cationic Peptides / metabolism Bacteria / growth & development Bacteria / immunology* Bacterial Infections / immunology* Bacterial Infections / metabolism Bacterial Infections / microbiology Drosophila Proteins / genetics Drosophila Proteins / immunology* Drosophila Proteins / metabolism Drosophila melanogaster / immunology Drosophila melanogaster / metabolism Drosophila melanogaster / microbiology Enterocytes / immunology Enterocytes / metabolism Enterocytes / microbiology Epithelial Cells / immunology* Epithelial Cells / metabolism Epithelial Cells / microbiology GATA Transcription Factors / genetics GATA Transcription Factors / immunology GATA Transcription Factors / metabolism Gene Expression Regulation / immunology Intestinal Mucosa / cytology NF-kappa B / immunology* NF-kappa B / metabolism Signal Transduction / immunology |
| IF | 21.522 |
| 引用数 | 15 |
| リソース情報 | |
| ショウジョウバエ | DGRC#109029 |