論文 - 詳細
RRC ID | 53529 |
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著者 | Najibi M, Labed SA, Visvikis O, Irazoqui JE. |
タイトル | An Evolutionarily Conserved PLC-PKD-TFEB Pathway for Host Defense. |
ジャーナル | Cell Rep |
Abstract |
The mechanisms that tightly control the transcription of host defense genes have not been fully elucidated. We previously identified TFEB as a transcription factor important for host defense, but the mechanisms that regulate TFEB during infection remained unknown. Here, we used C. elegans to discover a pathway that activates TFEB during infection. Gene dkf-1, which encodes a homolog of protein kinase D (PKD), was required for TFEB activation in nematodes infected with Staphylococcus aureus. Conversely, pharmacological activation of PKD was sufficient to activate TFEB. Furthermore, phospholipase C (PLC) gene plc-1 was also required for TFEB activation, downstream of Gαq homolog egl-30 and upstream of dkf-1. Using reverse and chemical genetics, we discovered a similar PLC-PKD-TFEB axis in Salmonella-infected mouse macrophages. In addition, PKCα was required in macrophages. These observations reveal a previously unknown host defense signaling pathway, which has been conserved across one billion years of evolution. |
巻・号 | 15(8) |
ページ | 1728-42 |
公開日 | 2016-5-24 |
DOI | 10.1016/j.celrep.2016.04.052 |
PII | S2211-1247(16)30479-X |
PMID | 27184844 |
PMC | PMC4880541 |
MeSH | Animals Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism* Caenorhabditis elegans / microbiology* Caenorhabditis elegans Proteins / metabolism Enzyme Activation Evolution, Molecular* Host-Pathogen Interactions / immunology* Macrophages / metabolism Macrophages / microbiology Mice Microbial Viability Protein Kinase C / metabolism* Protein Kinase C-alpha / metabolism RAW 264.7 Cells Salmonella enterica / physiology Signal Transduction* Staphylococcal Infections / enzymology Staphylococcal Infections / microbiology Staphylococcal Infections / pathology Staphylococcus aureus / physiology Type C Phospholipases / metabolism* |
IF | 7.815 |
引用数 | 26 |
リソース情報 | |
線虫 | tm1978 |