論文 - 詳細
| RRC ID | 53373 |
|---|---|
| 著者 | McEwan DL, Feinbaum RL, Stroustrup N, Haas W, Conery AL, Anselmo A, Sadreyev R, Ausubel FM. |
| タイトル | Tribbles ortholog NIPI-3 and bZIP transcription factor CEBP-1 regulate a Caenorhabditis elegans intestinal immune surveillance pathway. |
| ジャーナル | BMC Biol |
| Abstract |
BACKGROUND:Many pathogens secrete toxins that target key host processes resulting in the activation of immune pathways. The secreted Pseudomonas aeruginosa toxin Exotoxin A (ToxA) disrupts intestinal protein synthesis, which triggers the induction of a subset of P. aeruginosa-response genes in the nematode Caenorhabditis elegans. RESULTS:We show here that one ToxA-induced C. elegans gene, the Tribbles pseudokinase ortholog nipi-3, is essential for host survival following exposure to P. aeruginosa or ToxA. We find that NIPI-3 mediates the post-developmental expression of intestinal immune genes and proteins and primarily functions in parallel to known immune pathways, including p38 MAPK signaling. Through mutagenesis screening, we identify mutants of the bZIP C/EBP transcription factor cebp-1 that suppress the hypersusceptibility defects of nipi-3 mutants. CONCLUSIONS:NIPI-3 is a negative regulator of CEBP-1, which in turn negatively regulates protective immune mechanisms. This pathway represents a previously unknown innate immune signaling pathway in intestinal epithelial cells that is involved in the surveillance of cellular homeostasis. Because NIPI-3 and CEBP-1 are also essential for C. elegans development, NIPI-3 is analogous to other key innate immune signaling molecules such as the Toll receptors in Drosophila that have an independent role during development. |
| 巻・号 | 14(1) |
| ページ | 105 |
| 公開日 | 2016-12-7 |
| DOI | 10.1186/s12915-016-0334-6 |
| PII | 10.1186/s12915-016-0334-6 |
| PMID | 27927200 |
| PMC | PMC5143455 |
| MeSH | ADP Ribose Transferases / metabolism Animals Bacterial Toxins / metabolism Basic-Leucine Zipper Transcription Factors / genetics Basic-Leucine Zipper Transcription Factors / metabolism CCAAT-Enhancer-Binding Proteins / genetics CCAAT-Enhancer-Binding Proteins / metabolism* Caenorhabditis elegans / genetics* Caenorhabditis elegans / immunology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Exotoxins / metabolism Gastrointestinal Microbiome Gene Expression Regulation Immunity, Innate* Intestinal Mucosa / metabolism Intestines / microbiology Protein Biosynthesis Protein Kinases / genetics Protein Kinases / metabolism* Pseudomonas aeruginosa Signal Transduction Virulence Factors / metabolism p38 Mitogen-Activated Protein Kinases / genetics p38 Mitogen-Activated Protein Kinases / metabolism |
| IF | 6.765 |
| 引用数 | 7 |
| リソース情報 | |
| 線虫 | tm2807 tm4248 |