RRC ID 53529
Author Najibi M, Labed SA, Visvikis O, Irazoqui JE.
Title An Evolutionarily Conserved PLC-PKD-TFEB Pathway for Host Defense.
Journal 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.
Volume 15(8)
Pages 1728-42
Published 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
Times Cited 26
C.elegans tm1978