Reference - Detail
|Author||Najibi M, Labed SA, Visvikis O, Irazoqui JE.|
|Title||An Evolutionarily Conserved PLC-PKD-TFEB Pathway for Host Defense.|
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.
|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*|